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Cell. 2011 Apr 15;145(2):300-11. doi: 10.1016/j.cell.2011.03.034.

Activity-dependent IGF-1 exocytosis is controlled by the Ca(2+)-sensor synaptotagmin-10.

Author information

1
Department of Molecular and Cellular Physiology, and Howard Hughes Medical Institute, Stanford University, 1050 Arastradero Rd., Palo Alto, California 94305, USA.

Abstract

Synaptotagmins Syt1, Syt2, Syt7, and Syt9 act as Ca(2+)-sensors for synaptic and neuroendocrine exocytosis, but the function of other synaptotagmins remains unknown. Here, we show that olfactory bulb neurons secrete IGF-1 by an activity-dependent pathway of exocytosis, and that Syt10 functions as the Ca(2+)-sensor that triggers IGF-1 exocytosis in these neurons. Deletion of Syt10 impaired activity-dependent IGF-1 secretion in olfactory bulb neurons, resulting in smaller neurons and an overall decrease in synapse numbers. Exogenous IGF-1 completely reversed the Syt10 knockout phenotype. Syt10 colocalized with IGF-1 in somatodendritic vesicles of olfactory bulb neurons, and Ca(2+)-binding to Syt10 caused these vesicles to undergo exocytosis, thereby secreting IGF-1. Thus, Syt10 controls a previously unrecognized pathway of Ca(2+)-dependent exocytosis that is spatially and temporally distinct from Ca(2+)-dependent synaptic vesicle exocytosis controlled by Syt1. Our findings thereby reveal that two different synaptotagmins can regulate functionally distinct Ca(2+)-dependent membrane fusion reactions in the same neuron.

PMID:
21496647
PMCID:
PMC3102833
DOI:
10.1016/j.cell.2011.03.034
[Indexed for MEDLINE]
Free PMC Article
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