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Synapsin II and calcium regulate vesicle docking and the cross‐talk between vesicle pools at the mouse motor terminals
Author(s) -
Coleman William L.,
Bill Cynthia A.,
SimsekDuran Fatma,
Lonart György,
Samigullin Dmitry,
Bykhovskaia Maria
Publication year - 2008
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2008.154666
Subject(s) - synapsin i , synapsin , synaptic vesicle , vesicle , microbiology and biotechnology , neurotransmitter , chemistry , biology , biophysics , biochemistry , receptor , membrane
The synapsins, an abundant and highly conserved family of proteins that associate with synaptic vesicles, have been implicated in regulating the synaptic vesicle cycle. However, it has not been determined whether synapsin directly regulates the number of docked vesicles. Here we document that reducing Ca 2+ concentration [Ca 2+ ] o in the extracellular medium from 2 to 0.5 m m led to an approximately 40% decrease in both docked and undocked synaptic vesicles in wild‐type nerve terminals of the mouse diaphragm. The same treatment reduced the number of undocked vesicles in nerve terminals derived from synapsin II gene deleted animals, but surprisingly it did not decrease vesicle docking, indicating that synapsin II inhibits docking of synaptic vesicles at reduced [Ca 2+ ] o . In accordance with the morphological findings, at reduced [Ca 2+ ] o synapsin II (−) terminals had a higher rate of quantal neurotransmitter release. Microinjection of a recombinant synapsin II protein into synapsin II (−) terminals reduced vesicular docking and inhibited quantal release, indicating a direct and selective synapsin II effect for regulating vesicle docking and, in turn, quantal release. To understand why [Ca 2+ ] o has a prominent effect on synapsin function, we investigated the effect of [Ca 2+ ] o on the distribution of synaptic vesicles and on the concentration of intraterminal Ca 2+ . We found that reduced [Ca 2+ ] o conditions produce a decrease in intracellular Ca 2+ and overall vesicle depletion. To explore why at these conditions the role of synapsin II in vesicle docking becomes more prominent, we developed a quantitative model of the vesicle cycle, with a two step synapsin action in stabilizing the vesicle store and regulating vesicle docking. The results of the modelling were in a good agreement with the observed dependence of vesicle distribution on synapsin II and calcium deficiency.