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-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.
Neve
R L
RL
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Coopersmith
R
R
McPhie
D L
DL
Santeufemio
C
C
Pratt
K G
KG
Murphy
C J
CJ
Lynn
S D
SD
D001923:Brain Chemistry / Q000235:genetics; D002147:Calmodulin / Q000378:metabolism; D018076:DNA, Complementary / Q000302:isolation & purification; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000502:physiology; D005333:Fetus; D005455:Fluorescent Antibody Technique; D019922:GAP-43 Protein / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D015723:Gene Library; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D008854:Microscopy, Electron; D009474:Neurons / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D012333:RNA, Messenger / Q000032:analysis; D013572:Synaptic Vesicles / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D033921:Vesicular Transport Proteins
D002147:Calmodulin; D018076:DNA, Complementary; D019922:GAP-43 Protein; D008565:Membrane Proteins; C097227:RABEP1 protein, human; D012333:RNA, Messenger; D033921:Vesicular Transport Proteins