rhPlexin A4, CF (50 ug)

Background: Plexin A4

Plexin A4 is a 220‑230 kDa member of the plexin A subfamily, plexin family of proteins (1). It is found on sensory, autonomic and motor neurons and oligodendrocytes, plus T cells and dendritic cells (1‑8). Mature human Plexin A4 is an 1871 amino acid (aa) type I transmembrane glycoprotein with a 23 aa signal sequence, a 1214 aa extracellular domain (ECD), and a 636 aa cytoplasmic region. The ECD contains one Sema-domain (aa 51‑482), three PSI domains (aa 509‑856) and four IPT regions (aa 858‑1230) that contain a phosphoserine at aa 946 (1). Of three isoform variants, one shows a 65 aa substitution for aa 458‑1894, a second shows an 80 aa substitution for aa 1292‑1894, and a third shows the just mentioned 80 aa substitution coupled to a 14 aa substitution for aa 1‑535 (9). The human Plexin A4 ECD shares 97% aa identity with mouse, equine, canine, and bovine Plexin A4. Full‑length Plexin A4 also shares 67% aa identity with the most related family member, Plexin A2. Plexin A4 regulates cell migration, activation and axon guidance via repulsion (1‑5). It serves as a receptor for transmembrane semaphorins, Sema6A and 6B, and as a coreceptor with neuropilin-1 for the secreted semaphorin, Sema3A (1‑8). During development, it plays a role in nerve migration and midline crossing and down‑regulates dendrite formation (2‑8). It is often co‑expressed with Plexin A3, which can also engage class 6 semaphorins but prefers Sema3F/ neuropilin‑2 to Sema3A/neuropilin-1 (3, 8). Thus, Plexins A3 and A4 are redundant in some functions, but unique in others. In T cells, Plexin A4 engages Sema3A and negatively regulates TCR signals (6).