GAP43 stimulates inositol trisphosphate-mediated calcium release in response to hypotonicity
AUTOR(ES)
Caprini, Marco
FONTE
Oxford University Press
RESUMO
The identification of osmo/mechanosensory proteins in mammalian sensory neurons is still elusive. We have used an expression cloning approach to screen a human dorsal root ganglion cDNA library to look for proteins that respond to hypotonicity by raising the intracellular Ca2+ concentration ([Ca2+]i). We report the unexpected identification of GAP43 (also known as neuromodulin or B50), a membrane-anchored neuronal protein implicated in axonal growth and synaptic plasticity, as an osmosensory protein that augments [Ca2+]i in response to hypotonicity. Palmitoylation of GAP43 plays an important role in the protein osmosensitivity. Depletion of intracellular stores or inhibition of phospholipase C (PLC) activity abrogates hypotonicity-evoked, GAP43-mediated [Ca2+]i elevations. Notably, hypotonicity promoted the selective association of GAP43 with the PLC-δ1 isoform, and a concomitant increase in inositol-1,4,5-trisphosphate (IP3) formation. Collectively, these findings indicate that hypo-osmotic activation of GAP43 induces Ca2+ release from IP3-sensitive intracellular stores. The osmosensitivity of GAP43 furnishes a mechanistic framework that links axon elongation with phospho inositide metabolism, spontaneous triggering of cytosolic Ca2+ transients and the regulation of actin dynamics and motility at the growth cone in response to temporal and local mechanical forces.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=162146Documentos Relacionados
- Caffeine inhibits inositol trisphosphate-mediated liberation of intracellular calcium in Xenopus oocytes.
- Protein kinase C activators inhibit the inositol trisphosphate-mediated muscarinic current responses in rat lacrimal cells.
- Inhibition by Ca2+ of inositol trisphosphate-mediated Ca2+ liberation: a possible mechanism for oscillatory release of Ca2+.
- Inositol trisphosphate-mediated Ca2+ influx into Xenopus oocytes triggers Ca2+ liberation from intracellular stores.
- Ca2+ influx modulation of temporal and spatial patterns of inositol trisphosphate-mediated Ca2+ liberation in Xenopus oocytes.