Open AccessThe synaptotagmin juxtamembrane domain is involved in neuroexocytosis
Author(s) -
Caccin Paola,
Scorzeto Michele,
Damiano Nunzio,
Marin Oriano,
Megighian Aram,
Montecucco Cesare
Publication year - 2015
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1016/j.fob.2015.04.013
Subject(s) - synaptotagmin 1 , synaptic vesicle , vesicle fusion , axon terminal , microbiology and biotechnology , vesicle , transmembrane domain , biophysics , snap25 , chemistry , biology , biochemistry , membrane , axon
Synaptotagmin is a synaptic vesicle membrane protein which changes conformation upon Ca 2+ binding and triggers the fast neuroexocytosis that takes place at synapses. We have synthesized a series of peptides corresponding to the sequence of the cytosolic juxtamembrane domain of synaptotagmin, which is highly conserved among different isoforms and animal species, with or without either a hexyl hydrophobic chain or the hexyl group plus a fluorescein moiety. We show that these peptides inhibit neurotransmitter release, that they localize on the presynaptic membrane of the motor axon terminal at the neuromuscular junction and that they bind monophosphoinositides in a Ca 2+ ‐independent manner. Based on these findings, we propose that the juxtamembrane cytosolic domain of synaptotagmin binds the cytosolic layer of the presynaptic membrane at rest. This binding brings synaptic vesicles and plasma membrane in a very close apposition, favouring the formation of hemifusion intermediates that enable rapid vesicle fusion.