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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.
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JCS ePress
online publication date 14 Apr 2008
doi: 10.1242/jcs.022442
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121/9/1514
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Pathway selection to the axon depends on multiple targeting signals in NgCAM
* Author for correspondence (e-mail: BWinckler{at}virginia.edu)
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M. Ascano, A. Richmond, P. Borden, and R. Kuruvilla
Axonal Targeting of Trk Receptors via Transcytosis Regulates Sensitivity to Neurotrophin Responses
J. Neurosci.,
September 16, 2009;
29(37):
11674 - 11685.
[Abstract]
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© The Company of Biologists Ltd 2008