Role of the growth-associated protein B-50/GAP-43 in neuronal plasticity.
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.
Gispen
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WH
Rudolf Magnus Institute, University of Utrecht, The Netherlands.
Nielander
H B
HB
De Graan
P N
PN
Oestreicher
A B
AB
Schrama
L H
LH
Schotman
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P
D000595:Amino Acid Sequence; D000818:Animals; D002147:Calmodulin / Q000378:metabolism; D002148:Calmodulin-Binding Proteins; D003599:Cytoskeleton / Q000378:metabolism; D019922:GAP-43 Protein; D015870:Gene Expression; D005796:Genes; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D016716:PC12 Cells / Q000378:metabolism / Q000648:ultrastructure; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction
D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins