TY - JOUR
T1 - Inhibition of exocytosis or endocytosis blocks activity-dependent redistribution of synapsin
AU - Orenbuch, Ayelet
AU - Shulman, Yoav
AU - Lipstein, Noa
AU - Bechar, Amit
AU - Lavy, Yotam
AU - Brumer, Eliaz
AU - Vasileva, Mariya
AU - Kahn, Joy
AU - Barki-Harrington, Liza
AU - Kuner, Thomas
AU - Gitler, Daniel
N1 - https://doi.org/10.1111/j.1471-4159.2011.07579.x
PY - 2012
Y1 - 2012
N2 - J. Neurochem. (2012) 120, 248?258. Abstract The synaptic vesicle cycle encompasses the pre-synaptic events that drive neurotransmission. Influx of calcium leads to the fusion of synaptic vesicles with the plasma membrane and the release of neurotransmitter, closely followed by endocytosis. Vacated release sites are repopulated with vesicles which are then primed for release. When activity is intense, reserve vesicles may be mobilized to counteract an eventual decline in transmission. Recently, interplay between endocytosis and repopulation of the readily releasable pool of vesicles has been identified. In this study, we show that exo-endocytosis is necessary to enable detachment of synapsin from reserve pool vesicles during synaptic activity. We report that blockage of exocytosis in cultured mouse hippocampal neurons, either by tetanus toxin or by the deletion of munc13, inhibits the activity-dependent redistribution of synapsin from the pre-synaptic terminal into the axon. Likewise, perturbation of endocytosis with dynasore or by a dynamin dominant-negative mutant fully prevents synapsin redistribution. Such inhibition of synapsin redistribution occurred despite the efficient phosphorylation of synapsin at its protein kinase A/CaMKI site, indicating that disengagement of synapsin from the vesicles requires exocytosis and endocytosis in addition to phosphorylation. Our results therefore reveal hitherto unidentified feedback within the synaptic vesicle cycle involving the synapsin-managed reserve pool.
AB - J. Neurochem. (2012) 120, 248?258. Abstract The synaptic vesicle cycle encompasses the pre-synaptic events that drive neurotransmission. Influx of calcium leads to the fusion of synaptic vesicles with the plasma membrane and the release of neurotransmitter, closely followed by endocytosis. Vacated release sites are repopulated with vesicles which are then primed for release. When activity is intense, reserve vesicles may be mobilized to counteract an eventual decline in transmission. Recently, interplay between endocytosis and repopulation of the readily releasable pool of vesicles has been identified. In this study, we show that exo-endocytosis is necessary to enable detachment of synapsin from reserve pool vesicles during synaptic activity. We report that blockage of exocytosis in cultured mouse hippocampal neurons, either by tetanus toxin or by the deletion of munc13, inhibits the activity-dependent redistribution of synapsin from the pre-synaptic terminal into the axon. Likewise, perturbation of endocytosis with dynasore or by a dynamin dominant-negative mutant fully prevents synapsin redistribution. Such inhibition of synapsin redistribution occurred despite the efficient phosphorylation of synapsin at its protein kinase A/CaMKI site, indicating that disengagement of synapsin from the vesicles requires exocytosis and endocytosis in addition to phosphorylation. Our results therefore reveal hitherto unidentified feedback within the synaptic vesicle cycle involving the synapsin-managed reserve pool.
KW - endocytosis
KW - exocytosis
KW - fluorescence imaging
KW - reserve pool
KW - synapsin
KW - vesicle recycling
UR - http://www.scopus.com/inward/record.url?scp=84155171156&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2011.07579.x
DO - 10.1111/j.1471-4159.2011.07579.x
M3 - Article
SN - 0022-3042
VL - 120
SP - 248
EP - 258
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 2
ER -