Human Sortilin Alexa Fluor® 405-conjugated Antibody

Applications

Please Note: Optimal dilutions should be determined by each laboratory for each application. General Protocols are available in the Technical Information section on our website.

Preparation and Storage

Background: Sortilin

Sortilin (neurotensin receptor 3, glycoprotein 95) is a 95 kDa Type I transmembrane monomeric glycoprotein that is one of five known members of the mammalian vacuolar protein sorting 10p domain (Vps10p-D) family of sorting receptors (1, 2). Human preprosortilin is processed by signal sequence cleavage followed by propeptide cleavage at a furin recognition site. The cationic propeptide exhibits pH-dependent high affinity binding that blocks the Sortilin ligand binding site both pre‑ and post-cleavage (3). The extracellular/luminal sequence comprises the Vps10p domain, including 10 conserved cysteines (10 CC) essential for ligand binding (2). The cytoplasmic domain sorting motifs confer all trafficking during synthesis, targeting to lysosomes, endocytosis and Golgi-endosome transport; as little as 10% may be found on the cell surface (4). Mature human Sortilin shares 91% aa identity with mouse and rat Sortilin and 93% aa identity with dog. During murine development, sortilin is mainly expressed in the nervous system (5) where it is a receptor for neuropeptides including neurotensin, nerve growth factor (NGF) and brain‑derived neurotrophic factor (BDNF) (6-9). ProNGF (or the NGF propeptide alone) binds sortilin with much higher affinity (Kd ~5-8 nM) than does mature NGF (Kd ~90 nM). The complex of sortilin, pro-NGF and the receptor p75^ntr results in endocytosis of proNGF and induction of apoptosis (7). Similar results have been obtained with pro-BDNF and BDNF (8, 9). Sortilin is expressed in other tissues including testis, skeletal muscle and fat (1, 10). It is essential and sufficient for biogenesis of Glut4 storage vesicles necessary for insulin responsiveness in adipocytes (10). Sortilin also binds lipoprotein lipase (11), apoE (2) and RAP (1, 11). Binding is competitive, indicating that although unrelated, targets likely bind the same site.

Product Datasheets

Related Research Areas

• APP Processing and Amyloid Plaque Formation
• Diabetes
• Glucose Homeostasis
• Neurotrophin/Trk Family
• Receptor Tyrosine Kinases (RTKs)
• VPS10P-domain Family