title: SorCS3 does not require propeptide cleavage to bind nerve growth factor.
abstract: The functional properties of the Vps10p-domain receptor SorCS3 are undescribed. Here, we examine its processing and sorting in cellular transfectants, and analyze the binding of potential ligands to the purified receptor. We show that SorCS3 is synthesized as a proprotein and converted to its mature form by N-terminal propeptide cleavage in distal Golgi compartments. The propeptide is not a requirement for normal processing of the receptor and does not prevent ligands from binding to the SorCS3 precursor form. Expression of wt and chimeric receptors further suggests that SorCS3 predominates on the plasma membrane, exhibits slow internalization and does not engage in intracellular trafficking. SorCS3 emerges as a new neurotrophin binding Vps10p-domain receptor functionally distinct from its relatives Sortilin and SorLA.
authors.affiliation: Institute of Medical Biochemistry, Ole Worms Allé, bldg. 170, University of Aarhus, 8000 Aarhus C, Denmark.
authors.forename: U B
authors.initials: UB
authors.lastname: Westergaard
authors.forename: K
authors.initials: K
authors.lastname: Kirkegaard
authors.forename: E S
authors.initials: ES
authors.lastname: Sørensen
authors.forename: C
authors.initials: C
authors.lastname: Jacobsen
authors.forename: M S
authors.initials: MS
authors.lastname: Nielsen
authors.forename: C M
authors.initials: CM
authors.lastname: Petersen
authors.forename: P
authors.initials: P
authors.lastname: Madsen
mesh_terms: D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D006801:Humans; D008024:Ligands; D009414:Nerve Growth Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011956:Receptors, Cell Surface; D018013:Receptors, Neuropeptide / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: D008024:Ligands; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D018013:Receptors, Neuropeptide; C498347:SorCS3 protein, human