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Cysteines in the neuropilin‐2 MAM domain modulate receptor homooligomerization and signal transduction
Author(s) -
Barton Rachael,
Driscoll Alyssa,
Flores Samuel,
Mudbhari Durlav,
Collins Theresa,
Iovine M. Kathryn,
Berger Bryan W.
Publication year - 2015
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.22619
Subject(s) - semaphorin , homomeric , neuropilin , chemistry , signal transduction , neuropilin 1 , microbiology and biotechnology , transmembrane protein , zebrafish , angiogenesis , receptor , protein tyrosine phosphatase , biochemistry , biology , cancer research , vascular endothelial growth factor , gene , protein subunit , vegf receptors
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. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 104: 371–378, 2015.