Journal
JOURNAL OF CELL SCIENCE
Volume 121, Issue 9, Pages 1514-1525Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.022442
Keywords
transcytosis; L1 cell-adhesion molecule; axonal targeting; apical targeting; MDCK cells; LDLR
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Funding
- NIGMS NIH HHS [GM 070736] Funding Source: Medline
- NINDS NIH HHS [R01 NS045969, NS 045969] Funding Source: Medline
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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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