THE NEURONAL GROWTH-ASSOCIATED PROTEIN GAP-43 INTERACTS WITH RABAPTIN-5 AND PARTICIPATES IN ENDOCYTOSIS

Structural plasticity of nerve cells is a requirement for activity-dep endent changes in the brain. The growth-associated protein GAP-43 is t hought to be one determinant of such plasticity, although the molecula r 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 peri ods of low activity in the neurons. To identify the function of GAP-43 during activity-dependent increases in Ca2+ levels, when it is not bo und to calmodulin, we sought proteins with which GAP-43 interacts in t he 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 sy naptic vesicle recycling. Modulation of endocytosis by GAP-43, in asso ciation with rabaptin-5, may constitute a common molecular mechanism b y which GAP-43 regulates membrane dynamics during its known roles in a ctivity-dependent neurotransmitter release and neurite outgrowth.