Recombinant Human Protocadherin alpha 4 Protein, CF

Protocadherin alpha 4 (PCDHA4), also called CNR1 (cadherin‑related neuronal receptor 1) in mouse, is a 110 ‑ 120 kDa type I transmembrane glycoprotein in the protocadherin family of more than 70 calcium‑dependent adhesion/recognition molecules (1 ‑ 4). It is one of 14 isoforms encoded by a tandemly arranged gene cluster of protocadherin alpha genes, and is thus termed a clustered protocadherin. Isoforms show monoallelic and combinatorial expression in the synaptic membrane of differentiating neurons that is thought to contribute to neural pathway recognition and sorting (5 ‑ 7). All isoforms have a similar, but non‑identical extracellular region with 6 cadherin repeats, and a constant region at the C‑terminus within the cytoplasmic domain indicating that all mediates similar intracellular signaling (4). Splice variants lacking the cytoplasmic constant region are common in clustered protocadherins; for PCDHA4 such a variant (798 aa versus the full‑length 947 aa) has been described (4, 8). Protocadherins are widely expressed in neurons, localized to axons and synaptic junctions (5, 9). Crystal structures indicate that PCDHA4 and other clustered cadherins are not likely to participate in the homophilic adhesions that are typical of cadherins, but participate in heterophilic interactions with gamma ‑protocadherins in cis that are needed for surface expression of alpha ‑protocadherin molecules (10, 11). Within the extracellular domain, human PCDHA4 shares 84% and 83% aa sequence identity with mouse and rat PCDHA4, respectively. An RGD motif in the first cadherin repeat of mouse PCDHA is thought to mediate beta 1 integrin adhesion, but is not present in human PCDHA4 (8, 10, 12). alpha ‑ and gamma ‑protocadherin molecules can be cleaved by matrix metalloproteinases and presenilin to generate a soluble extracellular domain and an intracellular portion that may be involved in signaling (1, 2).