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© The Rockefeller University Press, 0021-9525/2003/9/1317 $5.00
The Journal of Cell Biology, Volume 162, Number 7, 1317-1328

Uncovering multiple axonal targeting pathways in hippocampal neurons

¹ Brookdale Department of Molecular, Cell, and Developmental Biology, Mount Sinai School of Medicine, New York, NY 10029
² Department of Cell Biology, Yale Medical School, New Haven, CT 06520

Address correspondence to Bettina Winckler, Department of Molecular, Cell, and Developmental Biology, Mount Sinai School of Medicine, One Gustave Levy Place, Box 1007, New York, NY 10029. Tel.: (212) 241-8619. Fax: (212) 860-1174. email: Bettina.Winckler{at}mssm.edu

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.

Key Words: L1; NgCAM; axonal targeting; transcytosis; neuronal polarity

H. Fölsch's present address is Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, 2205 Tech Drive, Evanston, IL 60208.

Abbreviations used in this paper: BFA, brefeldin A; DIV, days in vitro; MDCK, Madin-Darby canine kidney; PI, polarity index.

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