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Publication : A novel phenylalanine-based targeting signal directs telencephalin to neuronal dendrites.

First Author  Mitsui S Year  2005
Journal  J Neurosci Volume  25
Issue  5 Pages  1122-31
PubMed ID  15689548 Mgi Jnum  J:95983
Mgi Id  MGI:3528522 Doi  10.1523/JNEUROSCI.3853-04.2005
Citation  Mitsui S, et al. (2005) A novel phenylalanine-based targeting signal directs telencephalin to neuronal dendrites. J Neurosci 25(5):1122-31
abstractText  Neurons sort out a variety of functional molecules to appropriate subcellular destinations. Telencephalin (TLCN; intercellular adhesion molecule-5) is a cell adhesion molecule specifically localized to somatodendritic membranes in the telencephalic neurons. Here, we established a new in vivo strategy to analyze neuronal sorting mechanisms by ectopic expression of molecules of interest in the cerebellar Purkinje cells of transgenic mice. By using this system, we identified a novel dendritic targeting determinant in the cytoplasmic tail region of TLCN. A full-length TLCN ectopically expressed in the Purkinje cells was localized exclusively to dendrites but not to axons. In contrast, a deletion of cytoplasmic C-terminal 12 amino acids (residues 901-912) or a point mutation of Phe905 to Ala abrogated the dendrite-specific targeting with appearance of the truncated and point-mutated TLCN in both axons and dendrites. Furthermore, an addition of the C-terminal 17 amino acids (residues 896-912) of TLCN to an unrelated molecule (CD8) was sufficient for its specific targeting to dendrites in several types of neurons. Because the C-terminal region of TLCN does not contain any canonical dendritic targeting sequences such as the tyrosine-based motif or the dileucine motif, this study suggests a novel mechanism of protein trafficking to the dendritic compartment of neurons.
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