First published online April 23, 2008
Journal of Cell Science 121, 902e (2008)
© The Company of Biologists Limited
Mixed messages move NgCAM
Epithelial cells and neurons polarize into distinct plasma membrane domains – apical and basolateral domains, and axonal and somatodendritic domains, respectively. Transmembrane proteins are known to be secreted in a polarized manner in such cells, but the molecular bases for this polarized membrane trafficking are unclear. This group previously showed that the cell-adhesion molecule NgCAM, which is largely delivered to axons in neurons and to the apical surface in epithelia, travels to axons through an indirect transcytotic pathway via somatodendritic endosomes. Here, Bettina Winckler and colleagues (p. 1514) identify and characterize the signals that are used by NgCAM as it travels through this pathway. The authors determine that a previously identified basolateral tyrosine-based signal of NgCAM is also a sufficient somatodendritic targeting signal. Moreover, they identify a second, novel, axonal targeting signal in the cytoplasmic tail of NgCAM that is cis-dominant and must be inactivated for the axonal signal to be executed. This cytoplasmic axonal targeting signal also promotes apical trafficking of NgCAM in MDCK epithelial cells. The transcytotic routing of NgCAM to the axon therefore requires the sequential regulation of multiple sorting signals in the cytoplasmic tail of NgCAM.
Related articles in JCS:
- Pathway selection to the axon depends on multiple targeting signals in NgCAM
- Chan Choo Yap, Rita L. Nokes, Dolora Wisco, Eric Anderson, Heike Fölsch, and Bettina Winckler
JCS 2008 121: 1514-1525.
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