title: Cysteines in the neuropilin-2 MAM domain modulate receptor homooligomerization and signal transduction.
abstract: Neuropilins (NRPs) are transmembrane receptors involved in angiogenesis, lymphangiogenesis, and neuronal development as well as in cancer metastasis. Previous studies suggest that NRPs exist in heteromeric complexes with vascular endothelial growth factors (VEGFs) and VEGF receptors as well as plexins and semaphorins. We determined via site-directed mutagenesis and bioluminescent resonance energy transfer assays that a conserved cysteine (C711) in the Danio rerio NRP2a MAM (meprin, A-5 protein, and protein tyrosine phosphatase μ) domain modulates NRP2a homomeric interactions. Mutation of this residue also disrupts semaphorin-3F binding in NRP2a-transfected COS-7 cells and prevents the NRP2a overexpression effects in a zebrafish vascular model. Collectively, our results indicate the MAM domain plays an important role in defining the NRP2 homodimer structure, which is important for semaphorin-dependent signal transduction via NRP2.
authors: Department of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, Pennsylvania.
authors: Rachael
authors: R
authors: Barton
authors: Program in Bioengineering, Lehigh University, Bethlehem, Pennsylvania.
authors: Alyssa
authors: A
authors: Driscoll
authors: Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania.
authors: Samuel
authors: S
authors: Flores
authors: Department of Mechanical Engineering, Lehigh University, Bethlehem, Pennsylvania.
authors: Durlav
authors: D
authors: Mudbhari
authors: Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania.
authors: Theresa
authors: T
authors: Collins
authors: Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania.
authors: M Kathryn
authors: MK
authors: Iovine
authors: Department of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, Pennsylvania.|Program in Bioengineering, Lehigh University, Bethlehem, Pennsylvania.
authors: Bryan W
authors: BW
authors: Berger
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D039943:Neuropilin-2 / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization / Q000502:physiology*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000502:physiology*; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D039943:Neuropilin-2; D029961:Zebrafish Proteins; D003545:Cysteine
keywords: membrane proteins; neuropilin; receptor dimerization; signal transduction