Cell Biology

A Tale of Two Signals

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Science  26 Aug 2005:
Vol. 309, Issue 5739, pp. 1302
DOI: 10.1126/science.309.5739.1302b

The intracellular transport of membrane proteins requires cellular machinery that recognizes targeting signals that may be present within the cyto-plasmic, membrane, or extracellular domains of the protein. But some proteins contain multiple targeting signals, which need to be decoded sequentially to execute the correct protein itinerary. Anderson et al.have examined the signals in NgCAM, a cell adhesion molecule that is generally found in the axonal membrane of neurons, but is first transported to the dendrites. When expressed in an epithelial cell line, NgCAM is transported to the basolateral plasma membrane and then transcytosed to the apical surface, where it remains despite multiple rounds of endocytosis and reinsertion into the apical membrane. Why then, after endocytosis, does the protein not go back to the basolateral surface? The signal for baso-lateral targeting resides in the cytoplasmic domain of NgCAM and is recognized by an adaptor protein that ensures delivery of newly synthesized protein to the basolateral surface. This signal is masked by phosphorylation of a key tyrosine residue, which uncovers a cryptic apical targeting signal in the extracellular domain and also maintains the protein within a recycling cycle at the apical surface. — SMH

J. Cell Biol. 170,595 (2005).

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