Biochemical Society transactions最新文献

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.

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.

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.

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.

Intercellular communication is an essential hallmark of multicellular organisms for their development and adult tissue homeostasis. Over the past two decades, attention has been focused on communication mechanisms based on various membrane structures, as illustrated by the burst of scientific literature in the field of extracellular vesicles (EVs). These lipid bilayer-bound nano- or microparticles, as vehicle-like devices, act as regulators in various biological and physiological processes. When EVs are internalized by recipient cells, their membrane and cytoplasmic cargoes can interfere with cellular activities, affecting pathways that regulate cell proliferation, differentiation, and migration. In cancer, EVs can transfer oncogenic factors, stimulate neo-angiogenesis and immunosuppression, reprogram stromal cells, and confer drug resistance traits, thereby remodeling the surrounding microenvironment. Although the mechanisms underlying EV biogenesis and uptake are now better understood, little is known about the spatiotemporal mechanism(s) of their actions after internalization. In this respect, we have shown that a fraction of endocytosed EVs reaches the nuclear compartment via the VOR (VAP-A-ORP3-Rab7) complex-mediated docking of late endosomes to the outer nuclear membrane in the nucleoplasmic reticulum, positioning and facilitating the transfer of EV cargoes into the nucleoplasm via nuclear pores. Here, we highlight the EV heterogeneity, the cellular pathways governing EV release and uptake by donor and recipient cells, respectively, and focus on a novel intracellular pathway leading to the nuclear transfer of EV cargoes. We will discuss how to intercept it, which could open up new avenues for clinical applications in which EVs and other small extracellular particles (e.g., retroviruses) are implicated.

High-risk human papillomaviruses (HPVs) are responsible for almost all cervical cancer cases and a growing number of oropharyngeal and anogenital cancers. The primary HPV oncoproteins, E6 and E7, act together to manipulate multiple cellular pathways that can ultimately result in malignant transformation. This includes the deregulation of several signalling pathways that regulate cell proliferation, cell cycle progression and cell survival. Although multiple functions of HPV E6 and E7 in driving oncogenesis are well known, recent studies have uncovered novel oncogenic functions of the HPV oncoproteins, including the manipulation of emerging mechanisms of cancer development, such as epigenetic modifications, cellular plasticity and genomic instability. This review explores current advances in understanding how the HPV oncoproteins interact with these cellular processes, highlighting potential therapeutic targets in HPV-associated cancers.

Cells adjust their proliferation in response to extrinsic factors and nutrients. Such inputs must reach the cell cycle machinery to ensure proper cell proliferation. This minireview focuses on evidence suggesting that phosphorylating the T-loop domain of cyclin-dependent kinases may be a critical and conserved conduit for these external signals. Understanding this regulatory mechanism could provide crucial insights into how all eukaryotic cells integrate external information to decide whether or not to divide.

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.

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.

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.