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- Title
Neuronal calcium sensor-1 facilitates neuronal exocytosis through phosphatidylinositol 4-kinase.
- Authors
Qian Zheng; Bobich, Joseph A.; Vidugiriene, Jolanta; McFadden, Susanne C.; Thomas, Fairwell; Roder, John; Jeromin, Andreas
- Abstract
This work tested the theory that neuronal calcium sensor-1 (NCS-1) has effects on neurotransmitter release beyond its actions on membrane channels. We used nerve-ending preparations where membrane channels are bypassed through membrane permeabilization made by mechanical disruption or streptolysin-O. Nerve ending NCS-1 and phosphatidylinositol 4-kinase (PI4K) are largely or entirely particulate, so their concentrations in nerve endings remain constant after breaching the membrane. Exogenous, myristoylated NCS-1 stimulated nerve ending phosphatidylinositol 4-phosphate[PI(4)P] synthesis, but non-myristoylated-NCS-1 did not. The N-terminal peptide of NCS-1 interfered with PI(4)P synthesis, and with spontaneous and Ca2+-evoked release of both[3H]-norepinephrine (NA) and[14C]-glutamate (glu) in a concentration-dependent manner. An antibody raised against the N-terminal of NCS-1 inhibited perforated nerve ending PI(4)P synthesis, but the C-terminal antibody had no effects. Antibodies against the N- and C-termini of NCS-1 caused significant increases in mini/spontaneous/stimulation-independent release of[3H]-NA from perforated nerve endings, but had no effect on[14C]-glu release. These results support the idea that NCS-1 facilitates nerve ending neurotransmitter release and phosphoinositide production via PI4K and localizes these effects to the N-terminal of NCS-1. Combined with previous work on the regulation of channels by NCS-1, the data are consistent with the hypothesis that a NCS-1–PI4K (NP, neuropotentiator) complex may serve as an essential linker between lipid and protein metabolism to regulate membrane traffic and co-ordinate it with ion fluxes and plasticity in the nerve ending.
- Subjects
NERVOUS system; PEPTIDES; LIPIDS; PHOSPHOINOSITIDES; PHOSPHOLIPIDS; HYPOTHESIS
- Publication
Journal of Neurochemistry, 2005, Vol 92, Issue 3, p442
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2004.02897.x