Function
The heterodimer formed by NGFR and SORCS2 functions as receptor for the precursor forms of NGF (proNGF) and BDNF (proBDNF). ProNGF and proBDNF binding both promote axon growth cone collapse (in vitro). Plays a role in the regulation of dendritic spine density in hippocampus neurons. Required for normal neurite branching and extension in response to BDNF. Plays a role in BDNF-dependent hippocampal synaptic plasticity. Together with NGFR and NTRK2, is required both for BDNF-mediated synaptic long-term depression and long-term potentiation. ProNGF binding promotes dissociation of TRIO from the heterodimer, which leads to inactivation of RAC1 and/or RAC2 and subsequent reorganization of the actin cytoskeleton. Together with the retromer complex subunit VPS35, required for normal expression of GRIN2A at synapses and dendritic cell membranes. Required for normal expression of the amino acid transporter SLC1A1 at the cell membrane, and thereby contributes to protect cells against oxidative stress.; Does not promote Schwann cell apoptosis in response to proBDNF.; SorCS2 104 kDa chain and SorCS2 18 kDa chain together promote Schwann cell apoptosis in response to proBDNF.
Gene References into Functions
- Here the authors have characterized SorCS1, SorCS2 and SorCS3 using biochemical methods and electron microscopy. They found that their purified extracellular domains co-exist in stable dimeric and monomeric populations. PMID: 28827148
- Sortilin-related receptor CNS expressed 2 (SorCS2) is one of the vacuolar protein sorting 10 family proteins which may be involved in the disease process of amyotrophic lateral sclerosis PMID: 26420026
Subcellular Location
Cell membrane; Single-pass type I membrane protein. Cell projection. Cytoplasmic vesicle membrane; Single-pass type I membrane protein. Early endosome membrane. Recycling endosome membrane. Cell junction, synapse, synaptosome. Perikaryon. Cell projection, dendrite. Cell projection, dendritic spine. Cell junction, synapse, postsynaptic density membrane.
Protein Families
VPS10-related sortilin family, SORCS subfamily
Tissue Specificity
Detected on neurons in the caudate region. Detected on neurons in the hippocampus (at protein level). Highly expressed in brain and kidney. Detected at low levels in heart, liver, small intestine, skeletal muscle and thymus.