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GAP43 stimulates inositol trisphosphate‐mediated calcium release in response to hypotonicity
Author(s) -
Caprini Marco,
Gomis Ana,
Cabedo Hugo,
PlanellsCases Rosa,
Belmonte Carlos,
Viana Félix,
FerrerMontiel Antonio
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg294
Subject(s) - humanities , art
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 Ca 2+ concentration ([Ca 2+ ] 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 [Ca 2+ ] 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 [Ca 2+ ] i elevations. Notably, hypotonicity promoted the selective association of GAP43 with the PLC‐δ 1 isoform, and a concomitant increase in inositol‐1,4,5‐trisphosphate (IP 3 ) formation. Collectively, these findings indicate that hypo‐osmotic activation of GAP43 induces Ca 2+ release from IP 3 ‐sensitive intracellular stores. The osmosensitivity of GAP43 furnishes a mechanistic framework that links axon elongation with phospho inositide metabolism, spontaneous triggering of cytosolic Ca 2+ transients and the regulation of actin dynamics and motility at the growth cone in response to temporal and local mechanical forces.