PLXNA4A

Plexin-A4 is a is_associated_with::protein that in humans is encoded by the PLXNA4 is_associated_with::gene.

Function
Plexin A4 binds to neuropilin 1 (Nrp1) and neuropilin 2 (Nrp2) and transduces signals from Sema3A, Sema6A, and Sema6B. These Nrp-plexin and is_associated_with::semaphorin complexes initiate cascades that regulate diverse processes such as is_associated_with::axon pruning and repulsion, dendritic attraction and branching, regulation of cell migration, vascular remodeling, and is_associated_with::growth cone collapse. Both upregulation and downregulation of Plexin A4 has been observed following neural injury suggesting a dynamic role for Sema3A and Plexin A4 in neural maintenance and regeneration. Additionally, Sema3A and therefore its receptor, Plexin A4, have been implicated as possible components of fast-fatigable muscle fiber denervation in is_associated_with::ALS.

Structure
Plexin A4 has ~1890 is_associated_with::amino acids that include a likely signal sequence, is_associated_with::transmembrane domain, and 12 extracellular is_associated_with::N-linked glycosylation sites. It also contains domains consistent with other class A is_associated_with::plexins including a Sema domain, three "Met-related sequences"/cysteine clusters, three extracellular is_associated_with::glycine-is_associated_with::proline repeats, intracellular SP domains, and a putative intracellular is_associated_with::tyrosine kinase is_associated_with::phosphorylation site.

Tissue distribution
In the adult rat is_associated_with::central nervous system (CNS), plexin A4 was present in neurons and fibers throughout the brain and spinal cord, including is_associated_with::neocortex, is_associated_with::hippocampus, is_associated_with::lateral hypothalamus, is_associated_with::red nucleus, is_associated_with::facial nucleus, and the mesencephalic trigeminal nucleus. Fibers expressed Plexin A4 in the lateral septum, is_associated_with::nucleus accumbens, several is_associated_with::thalamic nuclei, is_associated_with::substantia nigra pars reticulata, is_associated_with::zona incerta, is_associated_with::pontine reticular formation, as well as in several is_associated_with::cranial nerve nuclei. Plexin A4 has been found in dorsal and, to a greater extent, ventral horns of the spinal cord. Both is_associated_with::motor neurons and is_associated_with::interneurons in the ventral horn express Plexin A4. Motor axons exiting via the is_associated_with::ventral roots and the ascending and descending is_associated_with::white matter tracts express Plexin A4. In is_associated_with::dorsal root ganglia, Plexin A4 is expressed in the neuronal cell bodies as well as the central and peripheral processes of those cells.