The Neuronal Growth-Associated Protein GAP-43 Interacts with Rabaptin-5 and Participates in Endocytosis

• Published in: The Journal of neuroscience 1998-10, Vol.18 (19), p.7757-7767
• Main Authors: Neve, Rachael L, Coopersmith, Robert, McPhie, Donna L, Santeufemio, Christopher, Pratt, Kara G, Murphy, Curran J, Lynn, Stephanie D
• Format: Article
• Language: English
• Subjects: Brain Chemistry - genetics; Calmodulin - metabolism; DNA, Complementary - isolation & purification; Endocytosis - physiology; Endosomes - physiology; Fetus; Fluorescent Antibody Technique; GAP-43 Protein - genetics; GAP-43 Protein - isolation & purification; GAP-43 Protein - metabolism; Gene Expression - physiology; Gene Library; Humans; Membrane Proteins - genetics; Membrane Proteins - isolation & purification; Membrane Proteins - metabolism; Microscopy, Electron; Neurons - chemistry; Neurons - metabolism; Neurons - ultrastructure; RNA, Messenger - analysis; Synaptic Vesicles - chemistry; Synaptic Vesicles - metabolism; Synaptic Vesicles - ultrastructure; Vesicular Transport Proteins
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.18-19-07757.1998

Structural plasticity of nerve cells is a requirement for activity-dependent changes in the brain. The growth-associated protein GAP-43 is thought to be one determinant of such plasticity, although the molecular mechanism by which it mediates dynamic structural alterations at the synapse is not known. GAP-43 is bound by calmodulin when Ca2+ levels are low, and releases the calmodulin when Ca2+ levels rise, suggesting that calmodulin may act as a negative regulator of GAP-43 during periods of low activity in the neurons. To identify the function of GAP-43 during activity-dependent increases in Ca2+ levels, when it is not bound to calmodulin, we sought proteins with which GAP-43 interacts in the presence of Ca2+. We show here that rabaptin-5, an effector of the small GTPase Rab5 that mediates membrane fusion in endocytosis, is one such protein. We demonstrate that GAP-43 regulates endocytosis and synaptic vesicle recycling. Modulation of endocytosis by GAP-43, in association with rabaptin-5, may constitute a common molecular mechanism by which GAP-43 regulates membrane dynamics during its known roles in activity-dependent neurotransmitter release and neurite outgrowth.