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Biochimica Et Biophysica Acta Aug 2003Work with Paramecium has contributed to the actual understanding of certain aspects of exocytosis regulation, including membrane fusion. The system is faster and more... (Review)
Review
Work with Paramecium has contributed to the actual understanding of certain aspects of exocytosis regulation, including membrane fusion. The system is faster and more synchronous than any other dense-core vesicle system described and its highly regular design facilitates correlation of functional and ultrastructural (freeze-fracture) features. From early times on, several crucial aspects of exocytosis regulation have been found in Paramecium cells, e.g. genetically controlled microdomains (with distinct ultrastructure) for organelle docking and membrane fusion, involvement of calmodulin in establishing such microdomains, priming by ATP, occurrence of focal fusion with active participation of integral and peripheral proteins, decay of a population of integral proteins ("rosettes", mandatory for fusion capacity) into subunits and their lateral dispersal during fusion, etc. The size of rosette particles and their dispersal upon focal fusion would be directly compatible with proteolipid V(0) subunits of a V-ATPase, much better than the size predicted for oligomeric SNARE pins (SCAMPs are unknown from Paramecium at this time). However, there are some restrictions for a straightforward interpretation of ultrastructural results. The rather pointed, nipple-like tip of the trichocyst membrane could accommodate only one (or very few) potential V(0) counterpart(s), while the overlaying domain of the cell membrane contains numerous rosette particles. Particle size is compatible with V(0), but larger than that assumed for the SNARE complexes. When membrane fusion is induced in the presence of antibodies against cell surface components, focal fusion is seen to occur with dispersing rosette particles but without dispersal of their subunits and without pore expansion. Clearly, this is required for completing fusion and pore expansion. After cloning SNARE and V(0) components in Paramecium (with increasing details becoming rapidly available), we may soon be able to address the question more directly, whether any of these components or some new ones to be detected, serve exocytotic and/or any other membrane fusions in Paramecium.
Topics: Animals; Calcium; Carrier Proteins; Cell Membrane; Exocytosis; Membrane Fusion; Membrane Proteins; N-Ethylmaleimide-Sensitive Proteins; Paramecium; SNARE Proteins; Secretory Vesicles; Vesicular Transport Proteins
PubMed: 12914959
DOI: 10.1016/s0167-4889(03)00092-2 -
Traffic (Copenhagen, Denmark) May 2016There is a fundamental gap in our understanding of how a eukaryotic cell apportions the limited space within its cell membrane. Upon infection, a cell competes with... (Review)
Review
There is a fundamental gap in our understanding of how a eukaryotic cell apportions the limited space within its cell membrane. Upon infection, a cell competes with intracellular pathogens for control of this same precious resource. The struggle between pathogen and host provides us with an opportunity to uncover the mechanisms regulating subcellular space by understanding how pathogens modulate vesicular traffic and membrane fusion events to create a specialized compartment for replication. By comparing several important intracellular pathogens, we review the molecular mechanisms and trafficking pathways that drive two space allocation strategies, the formation of tight and spacious pathogen-containing vacuoles. Additionally, we discuss the potential advantages of each pathogenic lifestyle, the broader implications these lifestyles might have for cellular biology and outline exciting opportunities for future investigation.
Topics: Host-Pathogen Interactions; Membrane Fusion; Vacuoles
PubMed: 26842840
DOI: 10.1111/tra.12382 -
Cellular and Molecular Life Sciences :... Feb 2018The mitochondrial network constantly changes and remodels its shape to face the cellular energy demand. In human cells, mitochondrial fusion is regulated by the large,... (Review)
Review
The mitochondrial network constantly changes and remodels its shape to face the cellular energy demand. In human cells, mitochondrial fusion is regulated by the large, evolutionarily conserved GTPases Mfn1 and Mfn2, which are embedded in the mitochondrial outer membrane, and by OPA1, embedded in the mitochondrial inner membrane. In contrast, the soluble dynamin-related GTPase Drp1 is recruited from the cytosol to mitochondria and is key to mitochondrial fission. A number of new players have been recently involved in Drp1-dependent mitochondrial fission, ranging from large cellular structures such as the ER and the cytoskeleton to the surprising involvement of the endocytic dynamin 2 in the terminal abscission step. Here we review the recent findings that have expanded the mechanistic model for the mitochondrial fission process in human cells and highlight open questions.
Topics: Animals; Humans; Membrane Fusion; Mitochondrial Dynamics; Mitochondrial Membranes; Mitochondrial Proteins
PubMed: 28779209
DOI: 10.1007/s00018-017-2603-0 -
Proceedings of the National Academy of... Jul 2014Over the past 20 years, it has been widely accepted that membrane fusion proceeds via a hemifusion step before opening of the productive fusion pore. An initial...
Over the past 20 years, it has been widely accepted that membrane fusion proceeds via a hemifusion step before opening of the productive fusion pore. An initial hourglass-shaped lipid structure, the fusion stalk, is formed between the adjacent membrane leaflets (cis leaflets). It remains controversial if and how fusion proteins drive the subsequent transition (expansion) of the stalk into a fusion pore. Here, we propose a comprehensive and consistent thermodynamic understanding in terms of the underlying free-energy landscape of stalk expansion. We illustrate how the underlying free energy landscape of stalk expansion and the concomitant pathway is altered by subtle differences in membrane environment, such as leaflet composition, asymmetry, and flexibility. Nonleaky stalk expansion (stalk widening) requires the formation of a critical trans-leaflet contact. The fusion machinery can mechanically enforce trans-leaflet contact formation either by directly enforcing the trans-leaflets in close proximity, or by (electrostatically) condensing the area of the cis leaflets. The rate of these fast fusion reactions may not be primarily limited by the energetics but by the forces that the fusion proteins are able to exert.
Topics: Cell Membrane; Membrane Fusion; Models, Chemical
PubMed: 25024174
DOI: 10.1073/pnas.1323221111 -
Journal of Cell Science May 2011Cytokinesis and abscission are complicated events that involve changes in membrane transport and cytoskeleton organization. We have used the combination of time-lapse...
Cytokinesis and abscission are complicated events that involve changes in membrane transport and cytoskeleton organization. We have used the combination of time-lapse microscopy and correlative high-resolution 3D tomography to analyze the regulation and spatio-temporal remodeling of endosomes and microtubules during abscission. We show that abscission is driven by the formation of a secondary ingression within the intracellular bridge connecting two daughter cells. The initiation and expansion of this secondary ingression requires recycling endosome fusion with the furrow plasma membrane and nested central spindle microtubule severing. These changes in endosome fusion and microtubule reorganization result in increased intracellular bridge plasma membrane dynamics and abscission. Finally, we show that central spindle microtubule reorganization is driven by localized microtubule buckling and breaking, rather than by spastin-dependent severing. Our results provide a new mechanism for mediation and regulation of the abscission step of cytokinesis.
Topics: Cytokinesis; Endosomes; HeLa Cells; Humans; I-kappa B Kinase; Membrane Fusion; Microscopy, Immunoelectron; Microtubules; R-SNARE Proteins; RNA Interference
PubMed: 21486954
DOI: 10.1242/jcs.081448 -
Traffic (Copenhagen, Denmark) Aug 2018The mitochondrion is a unique organelle that serves as the main site of ATP generation needed for energy in the cell. However, mitochondria also play essential roles in... (Review)
Review
The mitochondrion is a unique organelle that serves as the main site of ATP generation needed for energy in the cell. However, mitochondria also play essential roles in cell death through apoptosis and necrosis, as well as a variety of crucial functions related to stress regulation, autophagy, lipid synthesis and calcium storage. There is a growing appreciation that mitochondrial function is regulated by the dynamics of its membrane fusion and fission; longer, fused mitochondria are optimal for ATP generation, whereas fission of mitochondria facilitates mitophagy and cell division. Despite the significance of mitochondrial homeostasis for such crucial cellular events, the intricate regulation of mitochondrial fusion and fission is only partially understood. Until very recently, only a single mitochondrial fission protein had been identified. Moreover, only now have researchers turned to address the upstream machinery that regulates mitochondrial fusion and fission proteins. Herein, we review the known GTPases involved in mitochondrial fusion and fission, but also highlight recent studies that address the mechanisms by which these GTPases are regulated. In particular, we draw attention to a substantial new body of literature linking endocytic regulatory proteins, such as the retromer VPS35 cargo selection complex subunit, to mitochondrial homeostasis. These recent studies suggest that relationships and cross-regulation between endocytic and mitochondrial pathways may be more widespread than previously assumed.
Topics: Animals; GTP Phosphohydrolases; Homeostasis; Membrane Fusion; Mitochondria; Mitochondrial Dynamics; Mitochondrial Proteins; Protein Transport
PubMed: 29663589
DOI: 10.1111/tra.12573 -
Current Opinion in Cell Biology Feb 2007Cellular damage triggers rapid resealing of the plasma membrane and repair of the cortical cytoskeleton. Plasma membrane resealing results from calcium-dependent fusion... (Review)
Review
Cellular damage triggers rapid resealing of the plasma membrane and repair of the cortical cytoskeleton. Plasma membrane resealing results from calcium-dependent fusion of membranous organelles and the plasma membrane at the site of the damage. Cortical cytoskeletal repair results from local assembly of actin filaments (F-actin), myosin-2 and microtubules into an array that closes around the original wound site. Control of the cytoskeletal response is exerted by local activation of the small GTPases, Rho and Cdc42. Recent work has given insight into both the membrane fusion and cytoskeletal responses to plasma membrane damage and we propose that Rho GTPase activation results at least in part from the events that drive membrane repair.
Topics: Actins; Animals; Cell Membrane; Cytoskeleton; Humans; Membrane Fusion; Microtubules; Myosins; Wound Healing
PubMed: 17174083
DOI: 10.1016/j.ceb.2006.12.001 -
ELife Jun 2021Two proteins called Sec17 and Sec18 may have a larger role in membrane fusion than is commonly assumed in textbook models.
Two proteins called Sec17 and Sec18 may have a larger role in membrane fusion than is commonly assumed in textbook models.
Topics: Adenosine Triphosphatases; Membrane Fusion; SNARE Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Vesicular Transport Proteins
PubMed: 34137372
DOI: 10.7554/eLife.70298 -
Annual Review of Phytopathology Sep 2023Membrane trafficking pathways play a prominent role in plant immunity. The endomembrane transport system coordinates membrane-bound cellular organelles to ensure that... (Review)
Review
Membrane trafficking pathways play a prominent role in plant immunity. The endomembrane transport system coordinates membrane-bound cellular organelles to ensure that immunological components are utilized effectively during pathogen resistance. Adapted pathogens and pests have evolved to interfere with aspects of membrane transport systems to subvert plant immunity. To do this, they secrete virulence factors known as effectors, many of which converge on host membrane trafficking routes. The emerging paradigm is that effectors redundantly target every step of membrane trafficking from vesicle budding to trafficking and membrane fusion. In this review, we focus on the mechanisms adopted by plant pathogens to reprogram host plant vesicle trafficking, providing examples of effector-targeted transport pathways and highlighting key questions for the field to answer moving forward.
Topics: Membranes; Cell Membrane; Biological Transport; Blister; Membrane Fusion
PubMed: 37186899
DOI: 10.1146/annurev-phyto-021622-123232 -
Journal of Virology Mar 2019Host factors render cells susceptible to viral infection. One family of susceptibility factors, the tetraspanin proteins, facilitate enveloped virus entry by promoting... (Review)
Review
Host factors render cells susceptible to viral infection. One family of susceptibility factors, the tetraspanin proteins, facilitate enveloped virus entry by promoting virus-cell membrane fusion. They also facilitate viral egress from infected cells. In this Gem, we discuss recent insights into how tetraspanins assemble viral entry and exit platforms on cell membranes, and we speculate that tetraspanins contribute to nonviral membrane fusions by similar mechanisms.
Topics: Animals; Cell Membrane; Humans; Membrane Fusion; Tetraspanins; Virus Diseases; Virus Internalization
PubMed: 30567993
DOI: 10.1128/JVI.01429-17