Journal
JOURNAL OF CELL BIOLOGY
Volume 162, Issue 7, Pages 1317-1328Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200307069
Keywords
L1; NgCAM; axonal targeting; transcytosis; neuronal polarity
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Funding
- NCI NIH HHS [1 R 24 CA095823-01] Funding Source: Medline
- NIGMS NIH HHS [R01 GM029765, GM29765] Funding Source: Medline
- NINDS NIH HHS [R01 NS045969, 1 R01 NS045969-01] Funding Source: Medline
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Neuronal polarity is, at least in part, mediated by the differential sorting of membrane proteins to distinct domains, such as axons and somata/dendrites. We investigated the pathways underlying the subcellular targeting of NgCAM, a cell adhesion molecule residing on the axonal plasma membrane. Following transport of NgCAM kinetically, surprisingly we observed a transient appearance of NgCAM on the somatodendritic plasma membrane. Down-regulation of endocytosis resulted in loss of axonal accumulation of NgCAM, indicating that the axonal localization of NgCAM was dependent on endocytosis. Our data suggest the existence of a dendrite-to-axon transcytotic pathway to achieve axonal accumulation. NgCAM mutants with a point mutation in a crucial cytoplasmic tail motif (YRSL) are unable to access the transcytotic route. Instead, they were found to travel to the axon on a direct route. Therefore, our results suggest that multiple distinct pathways operate in hippocampal neurons to achieve axonal accumulation of membrane proteins.
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