ArticleThe EMBO journal2003
GAP43 stimulates inositol trisphosphate-mediated calcium release in response to hypotonicity.
Article in The EMBO journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 36 citations in OpenAlex.
- A Novel Palmitoylation-Related Molecular Signature for Predicting and Therapeutically Targeting Alzheimer's Disease.Molecular neurobiology · 2025Article
- Cryptic Splicing of GAP43 mRNA is a Novel Hallmark of TDP-43-Associated ALS and AD.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Roles of palmitoylation in axon growth, degeneration and regeneration.Journal of neuroscience research · 2017Review
- Lentiviral-mediated growth-associated protein-43 modification of bone marrow mesenchymal stem cells improves traumatic optic neuropathy in rats.Molecular medicine reports · 2015Article
- Calcium-activated chloride current expression in axotomized sensory neurons: what for?Frontiers in molecular neuroscience · 2012Article
- Issues about the physiological functions of prolyl oligopeptidase based on its discordant spatial association with substrates and inconsistencies among mRNA, protein levels, and enzymatic activity.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2009Review
- Evolution of insect proteomes: insights into synapse organization and synaptic vesicle life cycle.Genome biology · 2008Article
- Hypo-osmolar stress induces p75NTR expression by activating Sp1-dependent transcription.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2007Article
- Attenuation of TRPV1 by AMG-517 after nerve injury promotes peripheral axonal regeneration in rats.Molecular painArticle
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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-delta(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.
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