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SV2A and SV2C are not vesicular Ca2+ transporters but control glucose-evoked granule recruitment

Janz, Roger
Published in Journal of Cell Science. 2005, vol. 118, no. Pt 23, p. 5647-60
Abstract Synaptic vesicle protein 2 (SV2) is expressed in neuroendocrine cells as three homologous isoforms, SV2A, SV2B and SV2C. Ca2+-dependent function in exocytosis has been attributed to SV2A and SV2B, without elucidation of the mechanism. The role of SV2C has not yet been addressed. Here we characterize the three SV2 isoforms and define their involvement in regulated insulin secretion. SV2A and SV2C are associated with insulin-containing granules and synaptic-like-microvesicles (SLM) in INS-1E insulinoma and primary beta-cells, whereas SV2B is only present on SLM. Neither overexpression nor isoform-specific silencing of SV2A or SV2C by RNA interference modifies depolarization-triggered cytosolic [Ca2+] rises or secretory granule [Ca2+], measured with a VAMP-2 aequorin chimera. This strongly argues against any Ca2+ transport function of SV2. Moreover, up- or downregulation of these isoforms has no influence on K+-induced insulin release suggesting that SV2 does not affect the Ca2+-dependent step(s) of exocytosis. By contrast, glucose-elicited secretion is inhibited during the sustained rather than the early phase, placing the action of SV2 on the recruitment of granules from the reserve pool to the plasma membrane. This conclusion is reinforced by capacitance measurements in glucose-stimulated SV2C-deficient cells. Like capacitance, evoked and basal hormone release are attenuated more by silencing of SV2C compared with SV2A. This indicates only partial redundancy and highlights a key role for SV2C in the secretory process.
Keywords AnimalsCalcium/metabolismCell LineCell Membrane/drug effects/metabolismCricetinaeCytoplasmic Granules/drug effects/metabolismGene Expression RegulationGene SilencingGlucose/pharmacologyHuman Growth Hormone/secretionInsulin/secretionInsulin-Secreting Cells/metabolismMembrane Glycoproteins/genetics/metabolism/physiologyNerve Tissue Proteins/genetics/metabolism/physiologyPancreas/cytology/metabolismRNA Interference/physiologyRNA, Small Interfering/pharmacologyRats
PMID: 16306227
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IEZZI-BAKHTIARI, Mariella et al. SV2A and SV2C are not vesicular Ca2+ transporters but control glucose-evoked granule recruitment. In: Journal of Cell Science, 2005, vol. 118, n° Pt 23, p. 5647-60. https://archive-ouverte.unige.ch/unige:34530

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Deposited on : 2014-02-28

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