|Semaphorin 6C in Mouse Embryo. Semaphorin 6C was detected in immersion fixed frozen sections of mouse embryo (15 d.p.c) using Goat Anti-Mouse Semaphorin 6C Antigen Affinity-purified Polyclonal Antibody (Catalog # AF2108) at 5 µg/mL overnight at 4 °C. Tissue was stained using the Anti-Goat HRP-DAB Cell & Tissue Staining Kit (brown; Catalog # CTS008) and counterstained with hematoxylin (blue). Specific labeling was localized to the plasma membrane of neuronal cells. View our protocol for Chromogenic IHC Staining of Frozen Tissue Sections.|
Semaphorin 6C (Sema6C; previously Sema Y) is a 120 kDa member of the Semaphorin family of axon guidance molecules (1-3). The four known Class 6 semaphorins are type I transmembrane glycoproteins that are most like Class 1 invertebrate semaphorins in structure, and exhibit neuropilin-independent binding to specific plexin A receptors (1-3). Amino acid (aa) identity of Class 6 semaphorins is around 40% overall, but 53-64% within the Sema domain. Sema6C is expressed developmentally in subregions of the central and peripheral nervous systems, heart, and kidney, and primarily in skeletal muscle in adults (3, 4). Mouse Sema6C cDNA encodes 931 aa, including a 25 aa signal sequence, a 580 aa extracellular domain (ECD) including the Sema domain, a 21 aa transmembrane sequence and a 305 aa cytoplasmic portion. Alternate exon splicing creates a 923 aa short form (Sema6C.3) that is lacking aa 185-224 within the Sema domain, but contains 32 unique aa inserted at aa 586; postnatally, this form predominates in muscle (2, 3). The long form predominates in brain, especially in areas of increased plasticity (4). Mouse Sema6C ECD shares 98%, 92%, 92%, 92%, and 88% aa sequence identity with corresponding rat, human, porcine, equine, and canine sequences, respectively. Sema6C, along with Sema6D, is co-expressed with and binds to Plexin A1 (5). This interaction is thought to guide proprioceptive peripheral neurons by repulsion, excluding them from the superficial dorsal horn of the spinal cord (5). Sema6C is downregulated and redistributed following denervation or axotomy, potentially promoting regrowth (4, 6). In muscle, Sema6C is concentrated at neuromuscular junctions (6).
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