title: Calcium-induced exocytosis from actomyosin-driven, motile varicosities formed by dynamic clusters of organelles.
abstract: Varicosities are ubiquitous neuronal structures that appear as local swellings along neurites of invertebrate and vertebrate neurons. Surprisingly little is known about their cell biology. We use here cultured Aplysia neurons and demonstrate that varicosities are motile compartments that contain large clusters of organelles. The content of varicosities propagate along neurites within the plasma membrane "sleeve", split and merge, or wobble in place. Confocal imaging, retrospective immunolabeling, electron microscopy and pharmacological perturbations reveal that the motility of the varicosities' organelle content occurs in concert with an actin scaffold and is generated by actomyosin motors. Despite the motility of these organelle clusters within the cytoplasm along the neurites, elevation of the free intracellular calcium concentration within varicosities by trains of action potentials induces exocytosis followed by membrane retrieval. Our observations demonstrate that varicosities formed in the absence of postsynaptic cells behave as "ready to go" prefabricated presynaptic terminals. We suggest that the varicosities' motility serves to increase the probability of encountering a postsynaptic cell and to rapidly form a functional synapse.
authors.affiliation: Department of Neurobiology, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel.
authors.forename: Guy
authors.initials: G
authors.lastname: Malkinson
authors.forename: Zohar M
authors.initials: ZM
authors.lastname: Fridman
authors.forename: Dotan
authors.initials: D
authors.lastname: Kamber
authors.forename: Ada
authors.initials: A
authors.lastname: Dormann
authors.forename: Eli
authors.initials: E
authors.lastname: Shapira
authors.forename: Micha E
authors.initials: ME
authors.lastname: Spira
mesh_terms: D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000200:Action Potentials; D000205:Actomyosin / Q000378:metabolism*; D000818:Animals; D001048:Aplysia; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D005089:Exocytosis / Q000502:physiology*; D017952:Ganglia, Invertebrate / Q000166:cytology; D008561:Membrane Fusion / Q000502:physiology; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D024462:Myosin Type II / Q000378:metabolism; D016501:Neurites / Q000502:physiology / Q000648:ultrastructure; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D015388:Organelles / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology
chemical_list: D000199:Actins; D019384:Nucleic Acid Synthesis Inhibitors; D015638:Cytochalasin D; D000205:Actomyosin; D024462:Myosin Type II; D002118:Calcium