Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.13.12.5 (aequorin)
 1,451 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of dense core secretory vesicles in the control of cytosolic-free Ca(2+) concentrations ([Ca(2+)](c)) in neuronal and neuroendocrine cells is enigmatic. By constructing a vesicle-associated membrane protein 2-synaptobrevin.aequorin chimera, we show that in clonal pancreatic islet beta-cells: (a) increases in [Ca(2+)](c) cause a prompt increase in intravesicular-free Ca(2+) concentration ([Ca(2+)]SV), which is mediated by a P-type Ca(2+)-ATPase distinct from the sarco(endo) plasmic reticulum Ca(2+)-ATPase, but which may be related to the PMR1/ATP2C1 family of Ca(2+) pumps; (b) steady state Ca(2+) concentrations are 3-5-fold lower in secretory vesicles than in the endoplasmic reticulum (ER) or Golgi apparatus, suggesting the existence of tightly bound and more rapidly exchanging pools of Ca(2+); (c) inositol (1,4,5) trisphosphate has no impact on [Ca(2+)](SV) in intact or permeabilized cells; and (d) ryanodine receptor (RyR) activation with caffeine or 4-chloro-3-ethylphenol in intact cells, or cyclic ADPribose in permeabilized cells, causes a dramatic fall in [Ca(2+)](SV). Thus, secretory vesicles represent a dynamic Ca(2+) store in neuroendocrine cells, whose characteristics are in part distinct from the ER/Golgi apparatus. The presence of RyRs on secretory vesicles suggests that local Ca(2+)-induced Ca(2+) release from vesicles docked at the plasma membrane could participate in triggering exocytosis.
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PMID:Dense core secretory vesicles revealed as a dynamic Ca(2+) store in neuroendocrine cells with a vesicle-associated membrane protein aequorin chimaera. 1157 10

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.
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PMID:SV2A and SV2C are not vesicular Ca2+ transporters but control glucose-evoked granule recruitment. 1630 27