| First Author | O'Leary R | Year | 2011 |
| Journal | Mol Biol Cell | Volume | 22 |
| Issue | 22 | Pages | 4362-72 |
| PubMed ID | 21917590 | Mgi Jnum | J:183013 |
| Mgi Id | MGI:5317350 | Doi | 10.1091/mbc.E11-04-0283 |
| Citation | O'Leary R, et al. (2011) A variable cytoplasmic domain segment is necessary for gamma-protocadherin trafficking and tubulation in the endosome/lysosome pathway. Mol Biol Cell 22(22):4362-72 |
| abstractText | Clustered protocadherins (Pcdhs) are arranged in gene clusters (alpha, beta, and gamma) with variable and constant exons. Variable exons encode cadherin and transmembrane domains and ~90 cytoplasmic residues. The 14 Pcdh-alphas and 22 Pcdh-gammas are spliced to constant exons, which, for Pcdh-gammas, encode ~120 residues of an identical cytoplasmic moiety. Pcdh-gammas participate in cell-cell interactions but are prominently intracellular in vivo, and mice with disrupted Pcdh-gamma genes exhibit increased neuronal cell death, suggesting nonconventional roles. Most attention in terms of Pcdh-gamma intracellular interactions has focused on the constant domain. We show that the variable cytoplasmic domain (VCD) is required for trafficking and organelle tubulation in the endolysosome system. Deletion of the constant cytoplasmic domain preserved the late endosomal/lysosomal trafficking and organelle tubulation observed for the intact molecule, whereas deletion or excision of the VCD or replacement of the Pcdh-gammaA3 cytoplasmic domain with that from Pcdh-alpha1 or N-cadherin dramatically altered trafficking. Truncations or internal deletions within the VCD defined a 26-amino acid segment required for trafficking and tubulation in the endolysosomal pathway. This active VCD segment contains residues that are conserved in Pcdh-gammaA and Pcdh-gammaB subfamilies. Thus the VCDs of Pcdh-gammas mediate interactions critical for Pcdh-gamma trafficking. |
