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Annual Review of Physiology 2015Lysosomes are acidic compartments filled with more than 60 different types of hydrolases. They mediate the degradation of extracellular particles from endocytosis and of... (Review)
Review
Lysosomes are acidic compartments filled with more than 60 different types of hydrolases. They mediate the degradation of extracellular particles from endocytosis and of intracellular components from autophagy. The digested products are transported out of the lysosome via specific catabolite exporters or via vesicular membrane trafficking. Lysosomes also contain more than 50 membrane proteins and are equipped with the machinery to sense nutrient availability, which determines the distribution, number, size, and activity of lysosomes to control the specificity of cargo flux and timing (the initiation and termination) of degradation. Defects in degradation, export, or trafficking result in lysosomal dysfunction and lysosomal storage diseases (LSDs). Lysosomal channels and transporters mediate ion flux across perimeter membranes to regulate lysosomal ion homeostasis, membrane potential, catabolite export, membrane trafficking, and nutrient sensing. Dysregulation of lysosomal channels underlies the pathogenesis of many LSDs and possibly that of metabolic and common neurodegenerative diseases.
Topics: Animals; Exocytosis; Homeostasis; Humans; Ion Channels; Ions; Lysosomal Storage Diseases; Lysosomes; Membrane Potentials
PubMed: 25668017
DOI: 10.1146/annurev-physiol-021014-071649 -
Physiological Reviews Jan 2022The spermatozoon is a highly differentiated and polarized cell, with two main structures: the head, containing a haploid nucleus and the acrosomal exocytotic granule,... (Review)
Review
The spermatozoon is a highly differentiated and polarized cell, with two main structures: the head, containing a haploid nucleus and the acrosomal exocytotic granule, and the flagellum, which generates energy and propels the cell; both structures are connected by the neck. The sperm's main aim is to participate in fertilization, thus activating development. Despite this common bauplan and function, there is an enormous diversity in structure and performance of sperm cells. For example, mammalian spermatozoa may exhibit several head patterns and overall sperm lengths ranging from ∼30 to 350 µm. Mechanisms of transport in the female tract, preparation for fertilization, and recognition of and interaction with the oocyte also show considerable variation. There has been much interest in understanding the origin of this diversity, both in evolutionary terms and in relation to mechanisms underlying sperm differentiation in the testis. Here, relationships between sperm bauplan and function are examined at two levels: first, by analyzing the selective forces that drive changes in sperm structure and physiology to understand the adaptive values of this variation and impact on male reproductive success and second, by examining cellular and molecular mechanisms of sperm formation in the testis that may explain how differentiation can give rise to such a wide array of sperm forms and functions.
Topics: Animals; Biological Evolution; Exocytosis; Humans; Male; Mammals; Sperm-Ovum Interactions; Spermatozoa; Testis
PubMed: 33880962
DOI: 10.1152/physrev.00009.2020 -
Journal of Neurochemistry Jun 2016Regulated exocytosis is a multistage process involving a merger between the vesicle and the plasma membrane, leading to the formation of a fusion pore, a channel,... (Review)
Review
Regulated exocytosis is a multistage process involving a merger between the vesicle and the plasma membrane, leading to the formation of a fusion pore, a channel, through which secretions are released from the vesicle to the cell exterior. A stimulus may influence the pore by either dilating it completely (full-fusion exocytosis) or mediating a reversible closure (transient exocytosis). In neurons, these transitions are short-lived and not accessible for experimentation. However, in some neuroendocrine cells and astrocytes, initial fusion pores may reopen several hundred times, indicating their stability. Frequently, these pores are too narrow to pass luminal molecules to the extracellular space (unproductive exocytosis), but their diameter can dilate upon stimulation. To explain the stability of the initial narrow fusion pores, anisotropic membrane constituents with a non-axisymmetric shape were proposed to accumulate in the fusion pore membrane. Although the nature of these is unclear, they may consist of lipids and proteins, including SNAREs, which may facilitate and regulate the pre- and post-fusional stages of exocytosis. This review highlights models and experimental studies revealing mechanisms of fusion pore stabilization in a narrow, release unproductive state. The fusion pore is a channel that forms when the vesicle and the plasma membranes merge, and mediates the release of secretions from the vesicle lumen to the cell exterior. Frequently, these pores are too narrow to pass molecules to the extracellular space. Anisotropic membrane constituents with a non-axisymmetric shape were proposed to accumulate in the fusion pore membrane. This article is part of a mini review series on Chromaffin cells (ISCCB Meeting, 2015).
Topics: Animals; Calcium; Cell Membrane; Exocytosis; Humans; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; Membrane Fusion; Secretory Vesicles
PubMed: 26841731
DOI: 10.1111/jnc.13561 -
FEBS Letters Nov 2018
Topics: Animals; Biological Transport; Cell Membrane; Endocytosis; Exocytosis; Humans
PubMed: 30417372
DOI: 10.1002/1873-3468.13274 -
Journal of Neurochemistry Jun 2016Exocytosis is the process by which stored neurotransmitters and hormones are released via the fusion of secretory vesicles with the plasma membrane. It is a dynamic,... (Review)
Review
Exocytosis is the process by which stored neurotransmitters and hormones are released via the fusion of secretory vesicles with the plasma membrane. It is a dynamic, rapid and spatially restricted process involving multiple steps including vesicle trafficking, tethering, docking, priming and fusion. For many years great steps have been undertaken in our understanding of how exocytosis occurs in different cell types, with significant focus being placed on synaptic release and neurotransmission. However, this process of exocytosis is an essential component of cell signalling throughout the body and underpins a diverse array of essential physiological pathways. Many similarities exist between different cell types with regard to key aspects of the exocytosis pathway, such as the need for Ca(2+) to trigger it or the involvement of members of the N-ethyl maleimide-sensitive fusion protein attachment protein receptor protein families. However, it is also equally clear that non-neuronal cells have acquired highly specialized mechanisms to control the release of their own unique chemical messengers. This review will focus on several important non-neuronal cell types and discuss what we know about the mechanisms they use to control exocytosis and how their specialized output is relevant to the physiological role of each individual cell type. These include enteroendocrine cells, pancreatic β cells, astrocytes, lactotrophs and cytotoxic T lymphocytes. Non-neuronal cells have acquired highly specialized mechanisms to control the release of unique chemical messengers, such as polarised fusion of insulin granules in pancreatic β cells targeted towards the vasculature (top). This review discusses mechanisms used in several important non-neuronal cell types to control exocytosis, and the relevance of intermediate vesicle fusion pore states (bottom) and their specialized output to the physiological role of each cell type. These include enteroendocrine cells, pancreatic β cells, astrocytes, lactotrophs and cytotoxic T lymphocytes. This article is part of a mini review series on Chromaffin cells (ISCCB Meeting, 2015).
Topics: Animals; Cell Membrane; Endocrine System; Exocytosis; Membrane Fusion; Nerve Tissue Proteins; Neuroglia; Secretory Vesicles
PubMed: 26938142
DOI: 10.1111/jnc.13602 -
Frontiers in Immunology 2021
Topics: Biological Transport; Cell Membrane; Exocytosis; Genetic Predisposition to Disease; Humans; Immunologic Deficiency Syndromes; Mutation; Neoplasms
PubMed: 34659271
DOI: 10.3389/fimmu.2021.769815 -
Science Advances Sep 2023Extracellular vesicles (EVs) have been established to play important roles in cell-cell communication and shown promise as therapeutic agents. However, we still lack a...
Extracellular vesicles (EVs) have been established to play important roles in cell-cell communication and shown promise as therapeutic agents. However, we still lack a basic understanding of how cells respond upon exposure to EVs from different cell sources at various doses. Thus, we treated fibroblasts with EVs from 12 different cell sources at doses between 20 and 200,000 per cell, analyzed their transcriptional effects, and functionally confirmed the findings in various cell types in vitro, and in vivo using single-cell RNA sequencing. Unbiased global analysis revealed EV dose to have a more significant effect than cell source, such that high doses down-regulated exocytosis and up-regulated lysosomal activity. However, EV cell source-specific responses were observed at low doses, and these reflected the activities of the EV's source cells. Last, we assessed EV-derived transcript abundance and found that immune cell-derived EVs were most associated with recipient cells. Together, this study provides important insights into the cellular response to EVs.
Topics: Extracellular Vesicles; Exocytosis; Fibroblasts; Cell Communication
PubMed: 37656796
DOI: 10.1126/sciadv.adh1168 -
The Journal of General Physiology Apr 2019Ca-dependent secretion is a process by which important signaling molecules that are produced within a cell-including proteins and neurotransmitters-are expelled to the... (Review)
Review
Ca-dependent secretion is a process by which important signaling molecules that are produced within a cell-including proteins and neurotransmitters-are expelled to the extracellular environment. The cellular mechanism that underlies secretion is referred to as exocytosis. Many years of work have revealed that exocytosis in neurons and neuroendocrine cells is tightly coupled to Ca and orchestrated by a series of protein-protein/protein-lipid interactions. Here, we highlight landmark discoveries that have informed our current understanding of the process. We focus principally on reductionist studies performed using powerful model secretory systems and cell-free reconstitution assays. In recent years, molecular cloning and genetics have implicated the involvement of a sizeable number of proteins in exocytosis. We expect reductionist approaches will be central to attempts to resolve their roles. The will continue to be an outlet for much of this work, befitting its tradition of publishing strongly mechanistic, basic research.
Topics: Animals; Biological Transport; Calcium; Cell Membrane; Exocytosis; Liposomes; Signal Transduction
PubMed: 30782604
DOI: 10.1085/jgp.201812298 -
Proceedings of the National Academy of... May 2022Exocytosis and endocytosis are tightly coupled. In addition to initiating exocytosis, Ca2+ plays critical roles in exocytosis–endocytosis coupling in neurons and...
Exocytosis and endocytosis are tightly coupled. In addition to initiating exocytosis, Ca2+ plays critical roles in exocytosis–endocytosis coupling in neurons and nonneuronal cells. Both positive and negative roles of Ca2+ in endocytosis have been reported; however, Ca2+ inhibition in endocytosis remains debatable with unknown mechanisms. Here, we show that synaptotagmin-1 (Syt1), the primary Ca2+ sensor initiating exocytosis, plays bidirectional and opposite roles in exocytosis–endocytosis coupling by promoting slow, small-sized clathrin-mediated endocytosis but inhibiting fast, large-sized bulk endocytosis. Ca2+-binding ability is required for Syt1 to regulate both types of endocytic pathways, the disruption of which leads to inefficient vesicle recycling under mild stimulation and excessive membrane retrieval following intense stimulation. Ca2+-dependent membrane tubulation may explain the opposite endocytic roles of Syt1 and provides a general membrane-remodeling working model for endocytosis determination. Thus, Syt1 is a primary bidirectional Ca2+ sensor facilitating clathrin-mediated endocytosis but clamping bulk endocytosis, probably by manipulating membrane curvature to ensure both efficient and precise coupling of endocytosis to exocytosis.
Topics: Calcium; Endocytosis; Exocytosis; Neurons; Synaptic Transmission; Synaptotagmin I
PubMed: 35537054
DOI: 10.1073/pnas.2111051119 -
Traffic (Copenhagen, Denmark) Oct 2018A cell is able to sense the biomechanical properties of the environment such as the rigidity of the extracellular matrix and adapt its tension via regulation of plasma... (Review)
Review
A cell is able to sense the biomechanical properties of the environment such as the rigidity of the extracellular matrix and adapt its tension via regulation of plasma membrane and underlying actomyosin meshwork properties. The cell's ability to adapt to the changing biomechanical environment is important for cellular homeostasis and also cell dynamics such as cell growth and motility. Membrane trafficking has emerged as an important mechanism to regulate cell biomechanics. In this review, we summarize the current understanding of the role of cell mechanics in exocytosis, and reciprocally, the role of exocytosis in regulating cell mechanics. We also discuss how cell mechanics and membrane trafficking, particularly exocytosis, can work together to regulate cell polarity and motility.
Topics: Animals; Biomechanical Phenomena; Cell Membrane; Cell Movement; Cell Polarity; Exocytosis; Humans; Membrane Fusion; Protein Transport
PubMed: 29943478
DOI: 10.1111/tra.12584