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The Journal of Neuroscience, October 1, 1998, 18(19):7757-7767
The Neuronal Growth-Associated Protein GAP-43 Interacts with
Rabaptin-5 and Participates in Endocytosis
Rachael L.
Neve1, 2,
Robert
Coopersmith1, 2,
Donna L.
McPhie1, 2,
Christopher
Santeufemio2,
Kara G.
Pratt1, 2,
Curran J.
Murphy1, 2, and
Stephanie D.
Lynn1, 2
1 Department of Genetics, Harvard Medical
School, Boston, Massachusetts 02115, and 2 McLean
Hospital, Belmont, Massachusetts 02178
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.
Key words:
GAP-43; growth-associated protein; calmodulin; rabaptin-5; endocytosis; synaptic vesicle
Copyright © 1998 Society for Neuroscience 0270-6474/98/18197757-11$05.00/0
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