Biochemical Society Transactions[JOURNAL]
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200 papers
The fantastic voyage: primordial germ cell migration through the developing mouse embryo.
Goodwin K
Biochem Soc Trans · 2025 Jul · PMID 40676845 · Full text
During the early stages of embryonic development, a small population of cells is set aside to form the germline. These primordial germ cells (PGCs) are often specified separate in time and space from their eventual home,...
During the early stages of embryonic development, a small population of cells is set aside to form the germline. These primordial germ cells (PGCs) are often specified separate in time and space from their eventual home, the developing gonads. PGCs must therefore undertake a journey through the developing tissues of the embryo to reach their destination and ensure the fertility of the organism. Despite decades of interest in this topic and significant progress made in other model organisms, there is still very little known about how this migration is accomplished in the mouse or any other mammal. In this review, I explore over half a century of work examining this enigmatic cell and its voyage through the mouse embryo, interpreting these findings in light of recent discoveries in the field of cell migration. I discuss possible migration modes used by mouse PGCs, changes in their microenvironment that could influence migration, and roles the nucleus might play in their journey. With modern advances in microscopy and transgenic reporter mice, it is time to delve into this fascinating and important model of cell migration in vivo.
Progress in recapitulating morphogenesis of blood microvascular structures for microphysiological systems development.
Monroy-Romero AX, Hautefeuille M
Biochem Soc Trans · 2025 Jul · PMID 40676841 · Full text
Microphysiological systems (MPSs) are complex cell culture platforms, designed to closely replicate the cellular microenvironment of tissues under physiopathological conditions. A critical aspect of these systems is the...
Microphysiological systems (MPSs) are complex cell culture platforms, designed to closely replicate the cellular microenvironment of tissues under physiopathological conditions. A critical aspect of these systems is the integration of a vascular network, which facilitates nutrient exchange, supports heterotypic cell interactions, and increases culture viability. A top-down engineering approach, where a prefabricated scaffold is used to introduce endothelial cells, has been widely employed. However, promoting self-organization through a bottom-up paradigm has proven more effective in recapitulating the geometric features of microvasculature, particularly the network nature of it as the capillary diameters. In vivo vasculature formation occurs primarily through two self-organization processes: vasculogenesis and angiogenesis. These processes follow a series of co-ordinated and regulated steps, driven by microenvironmental cues such as cell identity and heterogeneity, soluble factor distribution, extracellular matrix composition and mechanics, and flow-induced mechanical strains. By incorporating these parameters into in vitro platforms, researchers can develop physiologically relevant vascularized MPS for applications in drug development and disease modeling. This review explores the key mechanisms underlying vascular self-organization and highlights how they are being integrated into tissue-specific MPS platforms to achieve vascularization, which enhances the potential of MPS for studying various physiological and pathological processes.
UBQLN2 in neurodegenerative disease: mechanistic insights and emerging therapeutic potential.
Matthews AM, Whiteley AM
Biochem Soc Trans · 2025 Aug · PMID 40663766 · Full text
Ubiquilins (UBQLNs) regulate cellular protein turnover by shuttling proteins, or 'clients', to the proteasome or autophagy pathways for degradation. Of the five different UBQLN genes in humans, UBQLN2 is the most highly...
Ubiquilins (UBQLNs) regulate cellular protein turnover by shuttling proteins, or 'clients', to the proteasome or autophagy pathways for degradation. Of the five different UBQLN genes in humans, UBQLN2 is the most highly expressed in the nervous system and muscle tissue and has been linked to multiple neurodegenerative diseases. In particular, point mutations of UBQLN2 cause an X-linked, dominant form of amyotrophic lateral sclerosis (ALS), ALS with frontotemporal dementia (ALS/FTD), or FTD. Failed protein degradation is a hallmark of many neurodegenerative diseases, including ALS and FTD; however, it is not clear exactly how ALS/FTD-associated UBQLN2 mutations contribute to pathogenesis. Recent studies have revealed the complexity of UBQLN2 biology and allow deeper understanding as to how UBQLN2 dysfunction may contribute to neurodegenerative disease. UBQLN2 is necessary for mitochondrial protein degradation and for regulating mitochondrial turnover, both of which are essential for motor neurons and have been implicated in the pathogenesis of ALS. Stress granule (SG) formation and regulation are also affected by UBQLN2 mutations, and their dysregulation may contribute to the toxic protein aggregation and SG changes observed in neurodegenerative disease. Finally, there are compelling links connecting UBQLN2 dysfunction with changes to downstream neuronal morphology, function, and behavior. This review will detail the emerging consensus on how UBQLN2 protects against neurodegenerative disease and will provide insights into potential therapeutic approaches.
The rise of AMPylation: from bacterial beginnings to modern implications in health and disease.
Mukherjee M, Sreelatha A
Biochem Soc Trans · 2025 Aug · PMID 40631560 · Full text
Protein AMPylation is a post-translational modification in which adenosine monophosphate (AMP) from ATP is covalently attached to a target protein via a phosphodiester bond. This reaction is catalyzed by AMPylases, a div...
Protein AMPylation is a post-translational modification in which adenosine monophosphate (AMP) from ATP is covalently attached to a target protein via a phosphodiester bond. This reaction is catalyzed by AMPylases, a diverse group of enzymes containing adenylyltransferase, filamentation induced by cyclic AMP (FIC), or kinase domains. As a reversible modification, AMPylation is dynamically regulated by both writer enzymes (AMPylases) and eraser enzymes (deAMPylases). Since its initial discovery in bacterial nitrogen metabolism in 1967, AMPylation has been recognized as a critical regulatory mechanism in both prokaryotic and eukaryotic systems. Recent studies link AMPylation to neurological disorders, diabetes, and cancer metastasis, underscoring its physiological and pathological significance. In this review, we present an overview of the discovery of AMPylases and deAMPylases, highlighting their role in cellular signaling, stress response, and host-pathogen interactions.
DIG-DUBs: mechanisms and functions of ISG15 deconjugation by human and viral cross-reactive ubiquitin proteases.
Bonacci T, Emanuele MJ
Biochem Soc Trans · 2025 Jul · PMID 40631552 · Full text
Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like protein and, as such, acts as a post-translational modifier that plays a critical role during bacterial and viral infections after interferon (IFN) production. As...
Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like protein and, as such, acts as a post-translational modifier that plays a critical role during bacterial and viral infections after interferon (IFN) production. As part of the innate immune system, ISG15 is strongly induced by type I IFNs, and its conjugation to intracellular proteins and viral proteins (ISGylation) allows cells to fight off infection. Importantly, ISGylation is a reversible process that is largely mediated by the cysteine protease USP18 (Ubp43 in mice). As a multifaceted protein, USP18 is a major negative regulator of IFN signaling and the predominant deISGylating enzyme in humans. However, in recent years, additional proteases such as USP16 and USP24 have been reported to also mediate ISG15 hydrolysis. Moreover, coronaviruses and other viral pathogens often encode proteases that possess deISGylating activity, which promotes viral infection by antagonizing ISGylation. Here, we review various enzymes and modes of action employed by human and viral proteases to regulate deISGylation under physiological or pathogenic conditions.
Effects and regulation of ACE2 and TMPRSS2 abundance in healthy humans and in patients with SARS-CoV-2.
Bach ML, Jensen BL
Biochem Soc Trans · 2025 Jul · PMID 40631549 · Full text
The present narrative review focuses on organ distribution, co-localization, age-, and sex-dependent changes in angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) and how such changes as...
The present narrative review focuses on organ distribution, co-localization, age-, and sex-dependent changes in angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) and how such changes associate with SARS-CoV-2 virus entry and disease severity in humans. ACE2 is a membrane-bound enzyme with lower abundance in children/young adults compared with elderly, with no protein abundance difference between ages 35-50 and >80 but higher in females at reproductive age. ACE2 locates predominantly in gastrointestinal (GI)-tract epithelia, kidney proximal tubules, male and female reproductive organs with very low levels in the lungs. Estrogen upregulates ACE2, which can be shed from cells into plasma by, for example ADAM17, while remaining active. TMPRSS2 is a membrane-associated serine protease with androgen dependence. The highest levels in humans are found in male reproductive organs, kidney, and GI-tract. Co-localization with ACE2 in alveolar type 2 cells is based mostly on in vitro studies. Documentation of clustering of ACE2 and TMPRSS2 in human tissues is scarce and best in oral-pharyngeal mucosa. In patients with mild-to-serious COVID-19 disease, there is no consistent change in circulating renin, aldosterone, ACE and ACE2 activities, angiotensin II (ANGII), and Ang1-7. Increased ANGII levels are reported in critically ill patients, while ACE2 is massively present in urine. Use of RAAS inhibitors is not associated with negative outcomes in patients with COVID-19. In conclusion, co-localization of ACE2 and TMPRSS2 in oral and airway epithelia may explain the primary route of infection for SARS-CoV-2 virus. Higher risk for serious disease in elderly males may not be accounted for by quantitative changes in the proteins.
Molecular insight on the role of the phosphoinositide PIP3 in regulating the protein kinases Akt, PDK1, and BTK.
Shaw AL, Burke JE
Biochem Soc Trans · 2025 Aug · PMID 40613782 · Full text
Protein kinases are master regulators of myriad processes in eukaryotic cells playing critical roles in growth, metabolism, cellular differentiation, and motility. A subclass of protein kinases is regulated by their abil...
Protein kinases are master regulators of myriad processes in eukaryotic cells playing critical roles in growth, metabolism, cellular differentiation, and motility. A subclass of protein kinases is regulated by their ability to be localized and activated by the phosphoinositide phosphatidylinositol (3,4,5)-trisphosphate (PIP3). This includes multiple members of the AGC and TEC family kinases, which contain PIP3 binding pleckstrin homology (PH) domains. It has been postulated that they can be activated by PIP3-mediated disruption of autoinhibitory interactions between their kinase domains and PH domains. There has been considerable controversy based on differing molecular models for how these kinases are regulated by lipid binding and post-translational modifications. This review focuses on understanding the molecular underpinnings for how the PH domains of these enzymes regulate kinase activity and what role PIP3 plays in pathway activation. A specific focus is on the integration of experimental data derived from X-ray crystallography, cryo-electron microscopy, and hydrogen deuterium exchange mass spectrometry along with recent advances in artifical intelligence enabled protein modeling. The main lipid-binding enzymes described are the AGC protein kinases 3-phosphoinositide-dependent kinase (PDK1) and Akt, and the TEC family kinase, Bruton's agammaglobulinemia tyrosine kinase (BTK).
Straight A's: protein acylation in the S-activation and autophagic degradation of NOD-like receptors.
Martin NR, Fairn GD
Biochem Soc Trans · 2025 Jul · PMID 40613780 · Full text
Over the past decade, S-acylation has emerged as a crucial regulator of several innate immune signaling pathways, with new insights continually being gained. S-acylation, a reversible post-translational modification, inv...
Over the past decade, S-acylation has emerged as a crucial regulator of several innate immune signaling pathways, with new insights continually being gained. S-acylation, a reversible post-translational modification, involves the attachment of fatty acyl chains to cysteine residues, influencing protein localization, function, and stability. In this mini-review, we examine the accumulating evidence of the role of S-acylation in regulating nucleotide oligomerization domain (NOD)-like receptors. NOD-like receptor subfamily P3 (NLRP3), a key player in inflammasome formation, undergoes S-acylation at specific cysteine residues, which are essential for its localization to the trans-Golgi network and other organelles. Various zinc finger Asp-His-His-Cys motif-containing (zDHHC) enzymes mediate this modification, with zDHHC5 being particularly important for activation and the ability of NLRP3 to interact with never in mitosis gene A (NIMA)-related protein kinase 7 (NEK7), promoting inflammasome assembly, caspase-1 activation, and pyroptosis. Alternatively, S-acylation by zDHHC12 targets NLRP3 for chaperone-mediated autophagy, preventing excessive inflammation. NOD2, another NLR, requires S-acylation for membrane localization and effective signaling via the NF-κB and mitogen-activated protein kinase pathways in response to peptidoglycan components. Dysregulation of S-acylation in NOD2 is associated with Crohn's Disease (hypo-acylated) and Blau syndrome/early-onset sarcoidosis (hyper-acylated). Soluble NOD2 lacking S-acylation is ubiquitinated and eliminated by the autophagic pathway. This review highlights the significance of understanding the S-acylation cycle and its regulatory mechanisms in developing potential therapeutic interventions for related inflammatory diseases. We also discuss unresolved questions regarding the S-acylation of NOD2 and NLRP3, as well as the regulation of S-acylation in general.
Computational modelling of aggressive B-cell lymphoma.
Jayawant ES, Vareli A, Pepper A … +3 more , Pepper C, Simoes F, Mitchell S
Biochem Soc Trans · 2025 Aug · PMID 40613779 · Full text
Decades of research into the molecular signalling determinants of B cell fates, and recent progress in characterising the genetic drivers of lymphoma, has led to a detailed understanding of B cell malignancies but also r...
Decades of research into the molecular signalling determinants of B cell fates, and recent progress in characterising the genetic drivers of lymphoma, has led to a detailed understanding of B cell malignancies but also revealed daunting heterogeneity. While current therapies for diffuse large B-cell lymphoma are effective for some patients, they are largely agnostic to the biology of each individual's disease, and approximately one third of patients experience relapsed/refractory disease. Consequently, the challenge is to understand how each patient's mutational burden and tumour microenvironment combine to determine their response to treatment; overcoming this challenge will improve outcomes in lymphoma. This mini review highlights how data-driven modelling, statistical approaches and machine learning are being used to unravel the heterogeneity of lymphoma. We review how mechanistic computational models provide a framework to embed patient data within knowledge of signalling. Focusing on recurrently dysregulated signalling networks in lymphoma (including NF-κB, apoptosis and the cell cycle), we discuss the application of state-of-the-art mechanistic models to lymphoma. We review recent advances in which computational models have demonstrated the power to predict prognosis, identify promising combination therapies and develop digital twins that can recapitulate clinical trial results. With the future of treatment for lymphoma poised to transition from one-size-fits-all towards personalised therapies, computational models are well-placed to identify the right treatments to the right patients, improving outcomes for all lymphoma patients.
Ceramide homeostasis in hepatic lipid droplets.
Robles-Martinez L, Morin KH, Nikolova-Karakashian M
Biochem Soc Trans · 2025 Apr · PMID 40605341 · Full text
Almost all eukaryotic cells have the capacity to form lipid droplets (LDs) in conditions of excess energy. Traditionally thought to be just inert fat reservoirs, LDs have recently emerged as important metabolic regulator...
Almost all eukaryotic cells have the capacity to form lipid droplets (LDs) in conditions of excess energy. Traditionally thought to be just inert fat reservoirs, LDs have recently emerged as important metabolic regulators of cellular stress response that buffer excess free fats and protect cells from lipotoxicity. Ceramide is a bioactive lipid that accumulates in metabolic tissues during fat oversupply. Emerging evidence suggests that sphingolipids and sphingolipid-metabolizing enzymes are found in the LDs and affect LD biogenesis and functions. This article aims to summarize the evidence, delineate some plausible functions of ceramide in hepatic LD biogenesis, and illustrate some of the challenges in this novel field of research. We focus on the biogenesis of LDs in hepatocytes, the parenchymal cells of the liver, because non-alcoholic fatty liver disease is the quintessential manifestation of metabolic stress caused by fat oversupply.
Regulation of neuronal ankyrin localization and function by post-translational modifications.
Bird KM, Jenkins PM
Biochem Soc Trans · 2025 Apr · PMID 40605340 · Full text
Ankyrins are a family of intracellular scaffolding proteins that control the subcellular localization of a host of critically important signaling proteins within neurons, including many proteins associated with neurologi...
Ankyrins are a family of intracellular scaffolding proteins that control the subcellular localization of a host of critically important signaling proteins within neurons, including many proteins associated with neurological disease. Ankyrin proteins are a vital component of the neuron. These scaffolding proteins must be spatially and temporally arranged to interact with their binding partners and facilitate proper neuronal signaling. Dysfunction of ankyrins is associated with neurodevelopmental disorders such as epilepsy and autism spectrum disorder. Despite the high degree of sequence similarity between ankyrin proteins, they display almost completely nonoverlapping localization and function. How ankyrins localize to the correct subcellular compartments to interact with their binding partners and complete their distinct roles remains poorly understood. Emerging evidence suggests that post-translational modifications may play a key part in this process. Some of the post-translational modifications that have been identified to regulate ankyrins are phosphorylation, ubiquitination, and palmitoylation. These modifications affect proper interactions, function, and localization of ankyrin proteins, which highlights their potential role in disease. This review will give an overview of neuronal ankyrins, and how post-translational modifications could be utilized to regulate protein localization and function in the context of neurological disease.
Single-molecule study of the dynamics of the molecular chaperone Hsp70 during the functional cycle.
Hu H, Yang M, Perrett S … +1 more , Wu S
Biochem Soc Trans · 2025 Apr · PMID 40605339 · Full text
The 70-kDa heat shock protein, Hsp70, is a key chaperone involved in cellular protein homeostasis. The structure of the Hsp70 protein family is highly conserved, including a nucleotide-binding domain (NBD) and a substrat...
The 70-kDa heat shock protein, Hsp70, is a key chaperone involved in cellular protein homeostasis. The structure of the Hsp70 protein family is highly conserved, including a nucleotide-binding domain (NBD) and a substrate-binding domain (SBD). ATP binding and hydrolysis in the NBD of Hsp70 regulates the binding and release of substrates in the SBD via interdomain allosteric communication. Growing evidence shows that the conformational dynamics of Hsp70 are crucial for its function, which are difficult to probe by traditional bulk-based methods. Single-molecule techniques are emerging as powerful tools to explore the dynamics of proteins that are obscured in bulk measurements. In this review, we summarize recent progress in the study of the molecular dynamics of Hsp70 and its interactions with cochaperones and substrates using single-molecule fluorescence spectroscopy and single-molecule force spectroscopy. We discuss how the application of single-molecule techniques facilitates a deeper understanding of the mechanistic details of the chaperone functions of Hsp70.
ESCRTing the RABs through conversion.
Solinger JA, Ott DP, Spang A
Biochem Soc Trans · 2025 Apr · PMID 40605338 · Full text
The endosomal system is essential for the intra- and intercellular communication in cells and multicellular organisms. It is involved in the secretion of signaling factors and serves as a venue for signaling receptors fr...
The endosomal system is essential for the intra- and intercellular communication in cells and multicellular organisms. It is involved in the secretion of signaling factors and serves as a venue for signaling receptors from the plasma membrane, which are endocytosed after ligand binding. Many internalized receptor-ligand complexes and numerous other endocytosed proteins arrive at the Rab5-positive early endosome, where they will be sorted. Cargoes marked with ubiquitin are bound by endosomal sorting complex required for transport (ESCRT)-0 and ESCRT-I complexes to initiate their degradation. The remaining cargoes are recycled back to the plasma membrane or the trans-Golgi network. To degrade ubiquitinated cargoes, the early endosome has to mature into a late endosomal structure, the multivesicular body (MVB). This procedure requires the Rab5-to-Rab7 conversion, mediated by the RABEX5-MON1/CCZ1 RabGEF cascade. Moreover, cargoes destined for degradation have to be packaged into intraluminal vesicles (ILVs) through ESCRT-III and Vps4. The matured late endosome or MVB finally fuses with a lysosome to degrade the cargo. Although ESCRT-mediated ILV formation and Rab conversion are well-characterized processes during endosome maturation, it remained until recently unclear whether these processes are connected. Lately, several studies were published illuminating the relationship of ESCRT functions and Rab conversion. Here, we review the current knowledge on the role of the ESCRT machinery in cargo degradation and RABEX5 regulation and MON1/CCZ1-mediated Rab conversion during endosome maturation. Moreover, we propose a model on the regulatory role of ESCRT functions during endosome maturation.
Recent advances in understanding the role of extracellular vesicles from probiotics in intestinal immunity signaling.
Kurata A, Uegaki K
Biochem Soc Trans · 2025 Apr · PMID 40605337 · Full text
The diverse functions of gut symbiotic bacteria are attracting attention for their potential as probiotics. Some of those bacteria release extracellular vesicles (EVs), spherical structures of approximately 20-400 nm in...
The diverse functions of gut symbiotic bacteria are attracting attention for their potential as probiotics. Some of those bacteria release extracellular vesicles (EVs), spherical structures of approximately 20-400 nm in diameter, outside their cell bodies. Recent research has significantly advanced our understanding of the physicochemical and biochemical properties, functions, and host-cell interactions of EVs released by probiotic bacteria used in food fermentation, such as lactic acid bacteria, bifidobacteria, butyric acid bacteria, and acetic acid bacteria. However, concerns have been raised regarding the use of these EVs as postbiotics. In this review, we discuss the newly discovered roles of EVs in the gut immune signaling and the challenges associated with their application as postbiotics.
Is the SPLUNC1-Orai1 axis a critical determinant of lung health?
Tarran R
Biochem Soc Trans · 2025 Jun · PMID 40589325 · Full text
Short palate lung and nasal epithelial clone 1 (SPLUNC1; gene name BPIFA1) is a secreted protein that is highly expressed in the nasopharyngeal and pulmonary systems. By data mining, we found that SPLUNC1 is also express...
Short palate lung and nasal epithelial clone 1 (SPLUNC1; gene name BPIFA1) is a secreted protein that is highly expressed in the nasopharyngeal and pulmonary systems. By data mining, we found that SPLUNC1 is also expressed in other organs, including the kidneys and the pituitary gland. SPLUNC1 is an asthma and cystic fibrosis gene modifier that also inversely correlates with the severity of bronchiectasis. Orai1 is a plasma membrane Ca2+ channel that is an essential regulator of the immune system. We previously found that SPLUNC1 binds to Orai1, causing it to be ubiquitinated, internalized and trafficked to the lysosome for degradation, thus reducing Ca2+ signaling. Here, we discuss how dysregulation of SPLUNC1-Orai1 interactions may contribute to hyperinflammation in multiple pulmonary diseases. We, and others, have also targeted Orai1 therapeutically, and we will also discuss how Orai1 inhibition may overcome SPLUNC1 deficiency and be beneficial for the treatment of chronic lung disease.
Regulation of adipogenesis by nucleotides.
Pinette JA, Bryant HG, Myers JW … +1 more , Zaganjor E
Biochem Soc Trans · 2025 Jun · PMID 40587264 · Full text
The process by which multipotent cells commit to differentiate into distinct cell types, eventually forming functional tissues and organisms, has fascinated scientists for decades. Consequently, numerous studies have con...
The process by which multipotent cells commit to differentiate into distinct cell types, eventually forming functional tissues and organisms, has fascinated scientists for decades. Consequently, numerous studies have contributed to our understanding of how transcription factors and signaling molecules regulate differentiation. A growing area of interest in the field centers around the role of nutrients and metabolic pathways in cell fate determination. This review focuses on adipogenesis (also termed hyperplasia), the formation of adipocytes, which are key sensors of nutrient availability. We will examine recent findings that reshape our understanding of how nucleotide metabolism regulates adipogenesis.
Connecting tubules: mechanisms of endoplasmic reticulum membrane fusion.
Jang E, Jun Y
Biochem Soc Trans · 2025 Jun · PMID 40587263 · Full text
Atlastins (ATLs) are integral dynamin-like GTPases that are critical for the formation and maintenance of the endoplasmic reticulum (ER) network, one of the most complex and essential organelles in eukaryotic cells. The...
Atlastins (ATLs) are integral dynamin-like GTPases that are critical for the formation and maintenance of the endoplasmic reticulum (ER) network, one of the most complex and essential organelles in eukaryotic cells. The ER, which is composed of interconnected tubules and sheets, serves vital functions, including calcium storage, protein and lipid synthesis, and inter-organelle communication. Homotypic membrane fusion, mediated by ATLs, ensures the tubular structure of the ER by generating and stabilizing three-way junctions. Humans express three ATL paralogs, called ATL1, ATL2, and ATL3, which have distinct expression patterns and regulatory mechanisms. Mutations in these proteins are linked to hereditary sensory neuropathies and hereditary spastic paraplegia, highlighting their critical importance in cellular and neuronal health. Here, we review recent studies providing insights into how ATLs are regulated by their N- and C-terminal extensions, as well as how extrinsic factors potentially regulate the activities of ATLs to establish and maintain the normal ER structure.
Understanding carboxysomes to enhance carbon fixation in crops.
Nguyen ND, Rourke LM, Cleaver A … +3 more , Brock J, Long BM, Price DG
Biochem Soc Trans · 2025 Jun · PMID 40570186 · Full text
Carboxysomes are bacterial microcompartments that enhance photosynthetic CO2 fixation by encapsulating ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) within a high-CO2 environment. Their modular, self-assembli...
Carboxysomes are bacterial microcompartments that enhance photosynthetic CO2 fixation by encapsulating ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) within a high-CO2 environment. Their modular, self-assembling nature makes them attractive for synthetic biology applications, particularly their transplantation alongside functional bicarbonate (HCO3-) transporters into plant chloroplasts to achieve improved photosynthetic efficiency. Recent advances have deepened our understanding of carboxysome biogenesis, Rubisco organisation and shell function. However, key questions remain, including the precise shell mechanistic action, which is critical for functional integration into new hosts. Addressing these questions, as well as identifying suitable bicarbonate transporters and fine-tuning expression levels, will be essential to utilising carboxysomes and the cyanobacterial CO2-concentrating mechanism for enhanced photosynthetic efficiency in crops.
How do different cell populations orchestrate myelin regeneration?
Grassi S, Prinetti A
Biochem Soc Trans · 2025 Jun · PMID 40552465 · Full text
Approximately 35 in 100,000 people are affected by diseases associated with loss of myelin, generally described as demyelinating diseases. Demyelinating diseases encompass many different pathological conditions character...
Approximately 35 in 100,000 people are affected by diseases associated with loss of myelin, generally described as demyelinating diseases. Demyelinating diseases encompass many different pathological conditions characterized by heterogeneous and sometimes disease-specific etiopathological mechanisms. While several approaches aimed at ameliorating the symptoms and the progression of some of these diseases exist, the most effective cure for all demyelinating diseases would be regeneration of lost myelin. Myelin regeneration occurs spontaneously in the central nervous system in response to myelin damage but is inefficient for a variety of reasons, especially in human patients. In this review, we will discuss the contributions of different cell populations to the creation of conditions permissive for effective remyelination and to the formation of new myelin after injury. Moreover, we would like to highlight the importance of sphingolipids in the network of interactions between these cell populations. Mutations in genes encoding sphingolipid metabolic enzymes (such as GALC) represent a major risk factor for multiple sclerosis, and alterations in sphingolipid metabolism in specific cell types contribute to myelin damage. On the other hand, sphingolipid signaling, in particular through sphingosine 1 phosphate, directly affects the process of myelin regeneration, with distinct effects on different cellular populations.
Single-molecule localisation microscopy approaches reveal envelope glycoprotein clusters in single-enveloped viruses: a potential functional role?
Williamson DJ, Zaza C, Carlon-Andres I … +10 more , Starling T, Gentili A, Thrush JW, Le Bas A, Ravi RT, Neil S, Owens RJ, Dumoux M, Simoncelli S, Padilla-Parra S
Biochem Soc Trans · 2025 Jun · PMID 40495469 · Full text
Understanding how viruses enter and fuse with host cells is crucial for developing effective antiviral therapies. The process of viral entry and fusion involves a series of complex steps that allow the virus to breach th...
Understanding how viruses enter and fuse with host cells is crucial for developing effective antiviral therapies. The process of viral entry and fusion involves a series of complex steps that allow the virus to breach the host cell membrane and deliver its genetic material inside, with viral fusogens often co-operating to attain the required energy for successful membrane fusion. This co-operative clustering of fusogens in viral envelopes is similar to receptor clustering in cellular systems, where receptors aggregate to initiate signalling cascades. Single-molecule localisation microscopy (SMLM) approaches have emerged as powerful tools to study these intricate mechanisms, allowing the observation of proteins with unprecedented levels of detail. These technologies provide unparalleled insights into the dynamics of viral entry and fusion at a molecular level, revealing how the co-ordinated action of fusogens facilitates membrane fusion. By employing the newest advances in SMLM techniques, such as DNA-PAINT and MINFLUX, we anticipate that precise information on the key steps of viral fusion can be revealed with high spatial and temporal resolutions, identifying critical points in the process that can be targeted by antiviral strategies.
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