Role of the growth-associated protein B-50/GAP-43 in neuronal plasticity

Abstract

The neuronal phosphoprotein B-50/GAP-43 has been implicated in neuritogenesis during developmental stages of the nervous system and in regenerative processes and neuronal plasticity in the adult. The protein appears to be a member of a family of acidic substrates of protein kinase C (PKC) that bind calmodulin at low calcium concentrations. Two of these substrates, B-50 and neurogranin, share the primary sequence coding for the phospho- and calmodulin-binding sites and might exert similar functions in axonal and dendritic processes, respectively. In the adult brain, B-50 is exclusively located at the presynaptic membrane. During neuritogenesis in cell culture, the protein is translocated to the growth cones, i.e., into the filopodia. In view of many positive correlations between B-50 expression and neurite outgrowth and the specific localization of B-50, a role in growth cone function has been proposed. Its phosphorylation state may regulate the local intracellular free calmodulin and calcium concentrations or vice versa. Both views link the B-50 protein to processes of signal transduction and transmitter release.

Determination of the endogenous phosphorylation state of B‐50/GAP‐43 and neurogranin in different brain regions by electrospray mass spectrometry

“…There is currently much debate on the role of B-50/GAP-43 in CNS function and particularly on its role in synaptic plasticity [5,6]. It has been proposed that in the induction phase of longterm potentiation (LTP, a cellular model for synaptic plasticity underlying learning and memory), an increased phosphorylation state of B-50/GAP-43 is observed and this increase could in turn induce an enhancement in neurotransmitter release [7,8].…”

The Cochlear Implant in Action: Molecular Changes Induced in the Rat Central Auditory System

“…The immediate early gene c-fos has, as part of its promoter, a transcription factor binding site called the cAMP response element (CRE; Ginty et al, 1994;Gispen et al, 1991). Thus, glutamate binding on NMDA receptors may activate the c-fos gene in neurons through the www.intechopen.com…”

Long-term potentiation and synaptic protein phosphorylation

“…B-50 (also known as growth-associated protein-43 (GAP-43), neuromodulin and F1; reviewed by: Liu and Storm [45]; Gispen et al [33]; Strittmatter et al [59]) is a well documented PKC substrate found predominantly in neurons at the cytosolic site of the presynaptic and the growth cone membrane, cDNA sequence analysis revealed rat B-50 as a 23.6-kDa protein of 226 amino acids with an apparent molecular weight of 43-48 kDa on SDS-PAGE. Palmitoylation of Cys-3 and/or Cys-4 of B-50 is important for its plasma membrane-association and is not required for its phosphorylation by PKC.…”