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Cold Spring Harbor Perspectives in... Oct 2021Hemagglutinins (HAs) are the receptor-binding and membrane fusion glycoproteins of influenza viruses. They recognize sialic acid-containing, cell-surface glycoconjugates... (Review)
Review
Hemagglutinins (HAs) are the receptor-binding and membrane fusion glycoproteins of influenza viruses. They recognize sialic acid-containing, cell-surface glycoconjugates as receptors but have limited affinity for them, and, as a consequence, virus attachment to cells requires their interaction with several virus HAs. Receptor-bound virus is transferred into endosomes where membrane fusion by HAs is activated at pH between 5 and 6.5, depending on the strain of virus. Fusion activity requires extensive rearrangements in HA conformation that include extrusion of a buried "fusion peptide" to connect with the endosomal membrane, form a bridge to the virus membrane, and eventually bring both membranes close together. In this review, we give an overview of the structures of the 16 genetically and antigenically distinct subtypes of influenza A HA in relation to these two functions in virus replication and in relation to recognition of HA by antibodies that neutralize infection.
Topics: Hemagglutinins; Humans; Hydrogen-Ion Concentration; Membrane Fusion; Orthomyxoviridae
PubMed: 32513673
DOI: 10.1101/cshperspect.a038638 -
Current Biology : CB Apr 2018A fundamental hallmark of eukaryotic cells is their compartmentalization into functionally distinct organelles, including those of the secretory and endocytic pathways.... (Review)
Review
A fundamental hallmark of eukaryotic cells is their compartmentalization into functionally distinct organelles, including those of the secretory and endocytic pathways. Transport of cargo between these compartments and to/from the cell surface is mediated by membrane-bound vesicles and tubules. Delivery of cargo is facilitated by SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor)-mediated membrane fusion of vesicles with their target compartments. Vesicles contain a variety of cargos, including lipids, membrane proteins, signaling molecules, biosynthetic and hydrolytic enzymes, and the trafficking machinery itself. Proper function of membrane trafficking is required for cellular growth, division, movement, and cell-cell communication. Defects in these processes have been implicated in a variety of human diseases, such as cancer, diabetes, neurodegenerative disorders, ciliopathies, and infections. The elucidation of the mechanisms of SNARE assembly and disassembly is key to understanding how membrane fusion is regulated throughout eukaryotes. Here, we introduce the SNARE proteins, their structures and functions in eukaryotic cells, and discuss recent breakthroughs in elucidating the regulation of SNARE assembly and disassembly through the use of high-resolution structural biology and biophysical techniques.
Topics: Animals; Biological Transport; Cell Membrane; Humans; Membrane Fusion; Protein Binding; Protein Transport; SNARE Proteins
PubMed: 29689222
DOI: 10.1016/j.cub.2018.01.005 -
The Journal of Cell Biology Oct 2021Fertilization is defined as the union of two gametes. During fertilization, sperm and egg fuse to form a diploid zygote to initiate prenatal development. In mammals,... (Review)
Review
Fertilization is defined as the union of two gametes. During fertilization, sperm and egg fuse to form a diploid zygote to initiate prenatal development. In mammals, fertilization involves multiple ordered steps, including the acrosome reaction, zona pellucida penetration, sperm-egg attachment, and membrane fusion. Given the success of in vitro fertilization, one would think that the mechanisms of fertilization are understood; however, the precise details for many of the steps in fertilization remain a mystery. Recent studies using genetic knockout mouse models and structural biology are providing valuable insight into the molecular basis of sperm-egg attachment and fusion. Here, we review the cell biology of fertilization, specifically summarizing data from recent structural and functional studies that provide insights into the interactions involved in human gamete attachment and fusion.
Topics: Cell Biology; Fertilization; Humans; Membrane Fusion
PubMed: 34459848
DOI: 10.1083/jcb.202102146 -
Current Biology : CB Apr 2018Segev et al. introduce fusogens - the proteins that coordinate, execute and control membrane fusion - and discuss their various physiological functions. (Review)
Review
Segev et al. introduce fusogens - the proteins that coordinate, execute and control membrane fusion - and discuss their various physiological functions.
Topics: Animals; Cell Fusion; Cell Membrane; Humans; Membrane Fusion; Membrane Proteins; Phospholipids
PubMed: 29689218
DOI: 10.1016/j.cub.2018.01.024 -
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 Open Bio Nov 2022Membrane fusion is not a spontaneous process. Physiologically, the formation of coiled-coil protein complexes, the SNAREpins, bridges the membrane of a vesicle and a... (Review)
Review
Membrane fusion is not a spontaneous process. Physiologically, the formation of coiled-coil protein complexes, the SNAREpins, bridges the membrane of a vesicle and a target membrane, brings them in close contact, and provides the energy necessary for their fusion. In this review, we utilize results from in vitro experiments and simple physics and chemistry models to dissect the kinetics and energetics of the fusion process from the encounter of the two membranes to the full expansion of a fusion pore. We find three main energy barriers that oppose the fusion process: SNAREpin initiation, fusion pore opening, and expansion. SNAREpin initiation is inherent to the proteins and makes in vitro fusion kinetic experiments rather slow. The kinetics are physiologically accelerated by effectors. The energy barriers that precede pore opening and pore expansion can be overcome by several SNAREpins acting in concert.
Topics: SNARE Proteins; Membrane Fusion; Kinetics; Models, Biological
PubMed: 35622519
DOI: 10.1002/2211-5463.13447 -
International Journal of Molecular... Jul 2022The superfamily of Ras proteins comprises different molecules belonging to the GTPase family. They normally cycle between an active state bound to GTP which activates... (Review)
Review
The superfamily of Ras proteins comprises different molecules belonging to the GTPase family. They normally cycle between an active state bound to GTP which activates effectors while the protein is membrane-associated, and an inactive GDP-bound state. They regulate the intracellular trafficking and other cellular processes. The family of Rab proteins includes several members and they have been found, among other Ras proteins, to be fundamental for important biological processes, such as endocytosis and exocytosis. SNARE proteins control the fusion of vesicles by forming quaternary complexes which are divided into two small groups on the two different compartments. Generally, the association of three SNARE proteins on the donor compartment with the one on the target compartment determines the formation of the SNARE complex, the opening of the fusion pore and the formation of one single bigger vesicle. Interestingly, novel interactions between other molecules involved in intracellular trafficking, endosomal fusion and maturation have recently been found, such as the interaction between invariant chain and the Qb SNARE vti1b, and more functional connections between Rab proteins and SNAREs are supposed to be fundamental for the regulation of membrane fusion.
Topics: Exocytosis; Membrane Fusion; Qb-SNARE Proteins; SNARE Proteins; ras Proteins
PubMed: 35897641
DOI: 10.3390/ijms23158067 -
The Journal of Membrane Biology Jun 2022Membrane fusion is an essential process for the survival of eukaryotes and the entry of enveloped viruses into host cells. A proper understanding of the mechanism of... (Review)
Review
Membrane fusion is an essential process for the survival of eukaryotes and the entry of enveloped viruses into host cells. A proper understanding of the mechanism of membrane fusion would provide us a handle to manipulate several biological pathways, and design efficient vaccines against emerging and re-emerging viral infections. Although fusion proteins take the central stage in catalyzing the process, role of lipid composition is also of paramount importance. Lipid composition modulates membrane organization and dynamics and impacts the lipid-protein (peptide) interaction. Moreover, the intrinsic curvature of lipids has strong impact on the formation of stalk and hemifusion diaphragm. Detection of transiently stable intermediates remains the bottleneck in the understanding of fusion mechanism. In order to circumvent this challenge, analytical methods can be employed to determine the kinetic parameters from ensemble average measurements of observables, such as lipid mixing, content mixing, and content leakage. The current review aims to present an analytical method that would aid our understanding of the fusion mechanism, provides a better insight into the role of lipid shape, and discusses the interplay of lipid and peptide in membrane fusion.
Topics: Kinetics; Lipids; Membrane Fusion; Peptides
PubMed: 35435451
DOI: 10.1007/s00232-022-00233-1 -
Nature Structural & Molecular Biology Jul 2008Subcellular compartmentalization, cell growth, hormone secretion and neurotransmission require rapid, targeted, and regulated membrane fusion. Fusion entails extensive... (Review)
Review
Subcellular compartmentalization, cell growth, hormone secretion and neurotransmission require rapid, targeted, and regulated membrane fusion. Fusion entails extensive lipid rearrangements by two apposed (docked) membrane vesicles, joining their membrane proteins and lipids and mixing their luminal contents without lysis. Fusion of membranes in the secretory pathway involves Rab GTPases; their bound 'effector' proteins, which mediate downstream steps; SNARE proteins, which can 'snare' each other, in cis (bound to one membrane) or in trans (anchored to apposed membranes); and SNARE-associated proteins (SM proteins; NSF or Sec18p; SNAP or Sec17p; and others) cooperating with specific lipids to catalyze fusion. In contrast, mitochondrial and cell-cell fusion events are regulated by and use distinct catalysts.
Topics: Animals; Cell Fusion; Membrane Fusion; Mitochondria; Models, Biological; Neurons; Synapses
PubMed: 18618939
DOI: 10.1038/nsmb.1451 -
Biochemical Society Transactions Aug 2022Visualization of cellular dynamics using fluorescent light microscopy has become a reliable and indispensable source of experimental evidence for biological studies.... (Review)
Review
Visualization of cellular dynamics using fluorescent light microscopy has become a reliable and indispensable source of experimental evidence for biological studies. Over the past two decades, the development of super-resolution microscopy platforms coupled with innovations in protein and molecule labeling led to significant biological findings that were previously unobservable due to the barrier of the diffraction limit. As a result, the ability to image the dynamics of cellular processes is vastly enhanced. These imaging tools are extremely useful in cellular physiology for the study of vesicle fusion and endocytosis. In this review, we will explore the power of stimulated emission depletion (STED) and confocal microscopy in combination with various labeling techniques in real-time observation of the membrane transformation of fusion and endocytosis, as well as their underlying mechanisms. We will review how STED and confocal imaging are used to reveal fusion and endocytic membrane transformation processes in live cells, including hemi-fusion; hemi-fission; hemi-to-full fusion; fusion pore opening, expansion, constriction and closure; shrinking or enlargement of the Ω-shape membrane structure after vesicle fusion; sequential compound fusion; and the sequential endocytic membrane transformation from flat- to O-shape via the intermediate Λ- and Ω-shape transition. We will also discuss how the recent development of imaging techniques would impact future studies in the field.
Topics: Cell Membrane; Endocytosis; Exocytosis; Membrane Fusion; Microscopy, Confocal; Secretory Vesicles
PubMed: 35960003
DOI: 10.1042/BST20210263