| First Author | Bonn S | Year | 2007 |
| Journal | Mol Cell Biol | Volume | 27 |
| Issue | 11 | Pages | 4121-32 |
| PubMed ID | 17403907 | Mgi Jnum | J:122331 |
| Mgi Id | MGI:3714084 | Doi | 10.1128/MCB.01708-06 |
| Citation | Bonn S, et al. (2007) Combinatorial expression of alpha- and gamma-protocadherins alters their presenilin-dependent processing. Mol Cell Biol 27(11):4121-32 |
| abstractText | Alpha- and gamma-protocadherins (Pcdhs) are type I transmembrane receptors expressed predominantly in the central nervous system and located in part in synapses. They are transcribed from complex genomic loci, giving rise in the mouse to 14 alpha-Pcdh and 22 gamma-Pcdh isoforms consisting of variable domains, each encompassing the extracellular region, the transmembrane region, and part of the intracellular region harboring the alpha- or gamma-Pcdh-specific invariant cytoplasmic domain. Presenilin-dependent intramembrane proteolysis (PS-IP) of gamma-Pcdhs and the formation of alpha/gamma-Pcdh heteromers led us to investigate the effects of homo- and heteromer formation on gamma- and putative alpha-Pcdh membrane processing and signaling. We find that upon surface delivery, alpha-Pcdhs, like gamma-Pcdhs, are subject to matrix metallo-protease cleavage followed by PS-IP in neurons. We further demonstrate that the combinatorial expression of alpha- and gamma-Pcdhs modulates the extent of their PS-IP, indicating the formation of alpha/gamma-Pcdh heteromers with an altered susceptibility to processing. Cell-specific expression of alpha/gamma-Pcdh isoforms could thus determine cell and synapse adhesive properties as well as intracellular and nuclear signaling by their soluble cytoplasmic cleavage products, alpha C-terminal fragment 2 (alpha-CTF-2) and gamma-CTF-2. |
