|SorCS3 in Mouse Brain. SorCS3 was detected in immersion fixed frozen sections of mouse brain (hippocampus) using 10 µg/mL Goat Anti-Mouse SorCS3 Antigen Affinity-purified Polyclonal Antibody (Catalog # AF3067) overnight at 4 °C. Tissue was stained with the NorthernLights™ 557-conjugated Anti-Goat IgG Secondary Antibody (red, upper panel; Catalog # NL001) and counterstained with DAPI (blue, lower panel). View our protocol for Fluorescent IHC Staining of Frozen Tissue Sections.|
SorCS3 is a type I transmembrane receptor of the mammalian Vps10p (vacuolar protein-sorting 10 protein) family of receptors that includes sortilin, SorLA, and three SorCS proteins (1, 2). It is synthesized as a 1219 amino acid (aa) preproform with a 33 aa signal sequence and a 100 aa propeptide. After proteolytic release of the propeptide at a furin-type consensus sequence, the mature SorCS3 is a 1086 aa, 100-110 kDa protein with a 992 aa extracellular/lumenal domain (ECD), a 21 aa transmembrane domain and a 73 aa cytoplasmic domain. Mouse SorCS3 ECD shares 98%, 92%, 91%, and 89% aa sequence identity with rat, human, bovine, and canine SorCS3 ECD, respectively. It also shares 65% and 44% aa identity with mouse SorCS1 and SorCS2 ECD, respectively. The ECD contains an imperfect leucine-rich repeat (LRR) and a Vps10p domain that binds both pro- and mature NGF (2, 3). The metalloproteinase TACE/ADAM17 is able to cleave SorCS3 near the membrane either constitutively, or at an increased rate when induced by phorbol esters (4). The shed ECD is able to bind PDGF-BB and the NGF propeptide (4). Unlike sortilin, the SorCS3 propeptide has no known function; it does not block NGF binding or propeptide cleavage (3, 5). SorCS3 is predominantly expressed on the plasma membrane (3). It can be slowly internalized but, despite the presence of a sorting domain, there is no evidence for SorCS3-mediated intracellular trafficking activity (3). It is expressed in the embryonic and adult central nervous system in areas distinct from that of SorCS1 and SorCS2 (1). Neuronal activity upregulates SorCS3 expression in the hippocampus (1).
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