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First published online 14 April 2008
doi: 10.1242/jcs.022442

Journal of Cell Science 121, 1514-1525 (2008)
Published by The Company of Biologists 2008
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Research Article

Pathway selection to the axon depends on multiple targeting signals in NgCAM

Chan Choo Yap1, Rita L. Nokes2,*, Dolora Wisco1,*, Eric Anderson{ddagger}, Heike Fölsch2 and Bettina Winckler1,§

1 University of Virginia Medical School, Department of Neuroscience, 409 Lane Road, Charlottesville, VA 22908, USA
2 Northwestern University, Department of Biochemistry, Molecular Biology and Cell Biology, 2205 Tech Drive, Evanston, IL 60208, USA

§ Author for correspondence (e-mail: BWinckler{at}virginia.edu)

Accepted 12 February 2008

Similar to most differentiated cells, both neurons and epithelial cells elaborate distinct plasma membrane domains that contain different membrane proteins. We have previously shown that the axonal cell-adhesion molecule L1/NgCAM accumulates on the axonal surface by an indirect transcytotic pathway via somatodendritic endosomes. MDCK epithelial cells similarly traffic NgCAM to the apical surface by transcytosis. In this study, we map the signals in NgCAM required for routing via the multi-step transcytotic pathway. We identify both a previously mapped tyrosine-based signal as a sufficient somatodendritic targeting signal, as well as a novel axonal targeting signal in the cytoplasmic tail of NgCAM. The axonal signal is glycine and serine rich, but only the glycine residues are required for activity. The somatodendritic signal is cis-dominant and needs to be inactivated in order for the axonal signal to be executed. Additionally, we show that the axonal cytoplasmic signal promotes apical targeting in MDCK cells. Transcytosis of NgCAM to the axon thus requires the sequential regulated execution of multiple targeting signals.

Key words: Transcytosis, L1 cell-adhesion molecule, Axonal targeting, Apical targeting, MDCK cells, LDLR


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