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The Journal of Neuroscience, February 15, 1999, 19(4):1324-1334
The sec6/8 Complex Is Located at Neurite Outgrowth and Axonal
Synapse-Assembly Domains
Christopher D.
Hazuka,
Davide L.
Foletti,
Shu-Chan
Hsu,
Yun
Kee,
F. Woodward
Hopf, and
Richard H.
Scheller
Department of Molecular and Cellular Physiology, Howard Hughes
Medical Institute, Stanford University School of Medicine, Stanford,
California 94305-5428
The molecules that specify domains on the neuronal plasma membrane
for the delivery and accumulation of vesicles during neurite outgrowth
and synapse formation are unknown. We investigated the role of the
sec6/8 complex, a set of proteins that specifies vesicle targeting
sites in yeast and epithelial cells, in neuronal membrane trafficking.
This complex was found in layers of developing rat brain undergoing
synaptogenesis. In cultured hippocampal neurons, the sec6/8 complex was
present in regions of ongoing membrane addition: the tips of growing
neurites, filopodia, and growth cones. In young axons, the sec6/8
complex was also confined to periodic domains of the plasma membrane.
The distribution of synaptotagmin, synapsin1, sec6, and FM1-43
labeling in cultured neurons suggested that the plasma membrane
localization of the sec6/8 complex preceded the arrival of synaptic
markers and was downregulated in mature synapses. We propose that the
sec6/8 complex specifies sites for targeting vesicles at domains of
neurite outgrowth and potential active zones during synaptogenesis.
Key words:
synaptogenesis; neurotransmission; secretion; exocytosis; synaptic vesicle; vesicle targeting
Copyright © 1999 Society for Neuroscience 0270-6474/99/1941324-11$05.00/0
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