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Current Topics in Membranes 2019The ability of repairing damages on the plasma membrane is crucial for cell survival. When damaged, eukaryotic cells are able to recover plasma membrane integrity within... (Review)
Review
The ability of repairing damages on the plasma membrane is crucial for cell survival. When damaged, eukaryotic cells are able to recover plasma membrane integrity within a few seconds, thus avoiding cytoplasm leakage and cell death. The process is driven by the influx of extracellular calcium which triggers a multitude of intracellular effects that participate in the process of plasma membrane resealing. One of the landmarks of plasma membrane repair is the triggering of intracellular vesicles recruitment and their exocytosis at damage sites. Since lysosomes are able to respond to calcium influx and that some of the lysosomal enzymes exocytosed after plasma membrane permeabilization are essential to restore cell integrity, these organelles have emerged as essential for the maintenance of plasma membrane integrity. Here we summarize the scientific evidences showing the involvement of lysosomes in plasma membrane repair that allowed researchers to propose a totally different function for this famous organelle.
Topics: Animals; Calcium; Cell Membrane; Endocytosis; Exocytosis; Humans; Lysosomes
PubMed: 31610859
DOI: 10.1016/bs.ctm.2019.08.001 -
Cell Research Sep 2016Necroptosis and pyroptosis are two forms of programmed cell death with a common feature of plasma membrane rupture. Here we studied the morphology and mechanism of...
Necroptosis and pyroptosis are two forms of programmed cell death with a common feature of plasma membrane rupture. Here we studied the morphology and mechanism of pyroptosis in comparison with necroptosis. Different from necroptosis, pyroptosis undergoes membrane blebbing and produces apoptotic body-like cell protrusions (termed pyroptotic bodies) prior to plasma membrane rupture. The rupture in necroptosis is explosion-like, whereas in pyroptosis it leads to flattening of cells. It is known that the execution of necroptosis is mediated by mixed lineage kinase domain-like (MLKL) oligomers in the plasma membrane, whereas gasdermin-D (GSDMD) mediates pyroptosis after its cleavage by caspase-1 or caspase-11. We show that N-terminal fragment of GSDMD (GSDMD-N) generated by caspase cleavage also forms oligomer and migrates to the plasma membrane to kill cells. Both MLKL and GSDMD-N are lipophilic and the N-terminal sequences of both proteins are important for their oligomerization and plasma membrane translocation. Unlike MLKL which forms channels on the plasma membrane that induces influx of selected ions which osmotically swell the cells to burst, GSDMD-N forms non-selective pores and does not rely on increased osmolarity to disrupt cells. Our study reveals the pore-forming activity of GSDMD and channel-forming activity of MLKL determine different ways of plasma membrane rupture in pyroptosis and necroptosis.
Topics: Amino Acids; Animals; Apoptosis Regulatory Proteins; Cell Line; Cell Membrane; Cell Membrane Permeability; Cell Shape; Humans; Intracellular Signaling Peptides and Proteins; Necrosis; Neoplasm Proteins; Phosphate-Binding Proteins; Protein Kinases; Protein Multimerization; Protein Transport; Pyroptosis; Structure-Activity Relationship
PubMed: 27573174
DOI: 10.1038/cr.2016.100 -
Human Genetics Aug 2023Exocytosis is the process by which secretory vesicles fuse with the plasma membrane to deliver materials to the cell surface or to release cargoes to the extracellular... (Review)
Review
Exocytosis is the process by which secretory vesicles fuse with the plasma membrane to deliver materials to the cell surface or to release cargoes to the extracellular space. The exocyst-an evolutionarily conserved octameric protein complex-mediates spatiotemporal control of SNARE complex assembly for vesicle fusion and tethering the secretory vesicles to the plasma membrane. The exocyst participates in diverse cellular functions, including protein trafficking to the plasma membrane, membrane extension, cell polarity, neurite outgrowth, ciliogenesis, cytokinesis, cell migration, autophagy, host defense, and tumorigenesis. Exocyst subunits are essential for cell viability; and mutations or variants in several exocyst subunits have been implicated in human diseases, mostly neurodevelopmental disorders and ciliopathies. These conditions often share common features such as developmental delay, intellectual disability, and brain abnormalities. In this review, we summarize the mutations and variants in exocyst subunits that have been linked to disease and discuss the implications of exocyst dysfunction in other disorders.
Topics: Humans; Vesicular Transport Proteins; Cytoplasm; Cell Membrane; Exocytosis; Nervous System Diseases
PubMed: 37085629
DOI: 10.1007/s00439-023-02558-w -
The Journal of Biological Chemistry Oct 2021Mitochondria are known as the powerhouses of eukaryotic cells; however, they perform many other functions besides oxidative phosphorylation, including Ca homeostasis,... (Review)
Review
Mitochondria are known as the powerhouses of eukaryotic cells; however, they perform many other functions besides oxidative phosphorylation, including Ca homeostasis, lipid metabolism, antiviral response, and apoptosis. Although other hypotheses exist, mitochondria are generally thought as descendants of an α-proteobacteria that adapted to the intracellular environment within an Asgard archaebacteria, which have been studied for decades as an organelle subdued by the eukaryotic cell. Nevertheless, several early electron microscopy observations hinted that some mitochondria establish specific interactions with certain plasma membrane (PM) domains in mammalian cells. Furthermore, recent findings have documented the direct physical and functional interaction of mitochondria and the PM, the organization of distinct complexes, and their communication through vesicular means. In yeast, some molecular players mediating this interaction have been elucidated, but only a few works have studied this interaction in mammalian cells. In addition, mitochondria can be translocated among cells through tunneling nanotubes or by other mechanisms, and free, intact, functional mitochondria have been reported in the blood plasma. Together, these findings challenge the conception of mitochondria as organelles subdued by the eukaryotic cell. This review discusses the evidence of the mitochondria interaction with the PM that has been long disregarded despite its importance in cell function, pathogenesis, and evolution. It also proposes a scheme of mitochondria-PM interactions with the intent to promote research and knowledge of this emerging pathway that promises to shift the current paradigms of cell biology.
Topics: Animals; Cell Membrane; Humans; Mitochondria
PubMed: 34481840
DOI: 10.1016/j.jbc.2021.101164 -
Current Opinion in Cell Biology Aug 2018Cell organelles and the plasma membrane have unique lipid compositions. Consequently, there is a gradient of lipid-dependent properties along the secretory pathway. We... (Review)
Review
Cell organelles and the plasma membrane have unique lipid compositions. Consequently, there is a gradient of lipid-dependent properties along the secretory pathway. We focus here on the steep sterol gradients that exist between the endoplasmic reticulum and plasma membrane, as well as across the plasma membrane where sterols are found principally in the cytoplasmic leaflet. Recent progress in these areas has been remarkable, with new concepts and molecules to account for non-vesicular intracellular sterol transport, and an exciting new mechanism to explain the unexpected transbilayer distribution of sterols.
Topics: Animals; Biological Transport; Cell Membrane; Endoplasmic Reticulum; Humans; Sterols; Yeasts
PubMed: 29783105
DOI: 10.1016/j.ceb.2018.04.012 -
Current Biology : CB Apr 2018Moseley discusses the molecular and mechanical functions of eisosomes - invaginations from the yeast plasma membrane. (Review)
Review
Moseley discusses the molecular and mechanical functions of eisosomes - invaginations from the yeast plasma membrane.
Topics: Cell Membrane; Cell Membrane Structures; Fungi; Phosphoproteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 29689217
DOI: 10.1016/j.cub.2017.11.073 -
Current Opinion in Cell Biology Aug 2018The compartmentalization of the plasma membrane is essential for cells to perform specialized biochemical functions, in particular those responsible for intracellular... (Review)
Review
The compartmentalization of the plasma membrane is essential for cells to perform specialized biochemical functions, in particular those responsible for intracellular and intercellular signaling pathways. Study of membrane compartmentalization requires state-of-the-art imaging tools that can reveal dynamics of individual molecules with high spatial and temporal resolution. In addition, quantitative analyses are employed to identify transient changes in molecule dynamics. In this review, membrane compartments are classified as stable domains, transient compartments, or nanodomains where proteins aggregate. Interestingly, in most cases, the cortical cytoskeleton plays important roles. Recent studies of the membrane-cytoskeleton interface are providing new insights about membrane organization involving a scale-free self-similar fractal structure and cytoskeleton active processes coupled to membrane dynamics.
Topics: Actins; Animals; Cell Membrane; Cytoskeleton; Humans; Membrane Proteins; Signal Transduction
PubMed: 29656224
DOI: 10.1016/j.ceb.2018.04.002 -
Cancer Metastasis Reviews Jun 2020Flotillins 1 and 2 are two ubiquitous, highly conserved homologous proteins that assemble to form heterotetramers at the cytoplasmic face of the plasma membrane in... (Review)
Review
Flotillins 1 and 2 are two ubiquitous, highly conserved homologous proteins that assemble to form heterotetramers at the cytoplasmic face of the plasma membrane in cholesterol- and sphingolipid-enriched domains. Flotillin heterotetramers can assemble into large oligomers to form molecular scaffolds that regulate the clustering of at the plasma membrane and activity of several receptors. Moreover, flotillins are upregulated in many invasive carcinomas and also in sarcoma, and this is associated with poor prognosis and metastasis formation. When upregulated, flotillins promote plasma membrane invagination and induce an endocytic pathway that allows the targeting of cargo proteins in the late endosomal compartment in which flotillins accumulate. These late endosomes are not degradative, and participate in the recycling and secretion of protein cargos. The cargos of this Upregulated Flotillin-Induced Trafficking (UFIT) pathway include molecules involved in signaling, adhesion, and extracellular matrix remodeling, thus favoring the acquisition of an invasive cellular behavior leading to metastasis formation. Thus, flotillin presence from the plasma membrane to the late endosomal compartment influences the activity, and even modifies the trafficking and fate of key protein cargos, favoring the development of diseases, for instance tumors. This review summarizes the current knowledge on flotillins and their role in cancer development focusing on their function in cellular membrane remodeling and vesicular trafficking regulation.
Topics: Animals; Carcinogenesis; Cell Membrane; Humans; Membrane Microdomains; Membrane Proteins; Neoplasms
PubMed: 32297092
DOI: 10.1007/s10555-020-09873-y -
The FEBS Journal Apr 2022Endocytosis is an essential cellular process required for multiple physiological functions, including communication with the extracellular environment, nutrient uptake,... (Review)
Review
Endocytosis is an essential cellular process required for multiple physiological functions, including communication with the extracellular environment, nutrient uptake, and signaling by the cell surface receptors. In a broad sense, endocytosis is accomplished through either constitutive or ligand-induced invagination of the plasma membrane, which results in the formation of the plasma membrane-retrieved endocytic vesicles, which can either be sent for degradation to the lysosomes or recycled back to the PM. This additional function of endocytosis in membrane retrieval has been adopted by excitable cells, such as neurons, for membrane equilibrium maintenance at synapses. The last two decades were especially productive with respect to the identification of brain-specific functions of the endocytic machinery, which additionally include but not limited to regulation of neuronal differentiation and migration, maintenance of neuron morphology and synaptic plasticity, and prevention of neurotoxic aggregates spreading. In this review, we highlight the current knowledge of brain-specific functions of endocytic machinery with a specific focus on three brain cell types, neuronal progenitor cells, neurons, and glial cells.
Topics: Brain; Cell Membrane; Endocytosis; Lysosomes; Synapses
PubMed: 33896112
DOI: 10.1111/febs.15897 -
Journal of Cell Science Sep 2018Clathrin-mediated endocytosis is an essential cellular mechanism by which all eukaryotic cells regulate their plasma membrane composition to control processes ranging... (Review)
Review
Clathrin-mediated endocytosis is an essential cellular mechanism by which all eukaryotic cells regulate their plasma membrane composition to control processes ranging from cell signaling to adhesion, migration and morphogenesis. The formation of endocytic vesicles and tubules involves extensive protein-mediated remodeling of the plasma membrane that is organized in space and time by protein-protein and protein-phospholipid interactions. Recent studies combining high-resolution imaging with genetic manipulations of the endocytic machinery and with theoretical approaches have led to novel multifaceted phenomenological data of the temporal and spatial organization of the endocytic reaction. This gave rise to various - often conflicting - models as to how endocytic proteins and their association with lipids regulate the endocytic protein choreography to reshape the plasma membrane. In this Review, we discuss these findings in light of the hypothesis that endocytic membrane remodeling may be determined by an interplay between protein-protein interactions, the ability of proteins to generate and sense membrane curvature, and the ability of lipids to stabilize and reinforce the generated membrane shape through adopting their lateral distribution to the local membrane curvature.
Topics: Animals; Cell Membrane; Clathrin; Endocytosis; Humans; Transport Vesicles
PubMed: 30177505
DOI: 10.1242/jcs.216812