PUBLICATION
Cysteines in the neuropilin-2 MAM domain modulate receptor homooligomerization and signal transduction
- Authors
- Barton, R., Driscoll, A., Flores, S., Mudbhari, D., Collins, T., Iovine, M.K., Berger, B.W.
- ID
- ZDB-PUB-150207-3
- Date
- 2015
- Source
- Biopolymers 104(4): 371-8 (Journal)
- Registered Authors
- Iovine, M. Kathryn
- Keywords
- Membrane proteins, neuropilin, receptor dimerization, signal transduction
- MeSH Terms
-
- Animals
- COS Cells
- Chlorocebus aethiops
- Cysteine/genetics
- Cysteine/metabolism
- Neuropilin-2/genetics
- Neuropilin-2/metabolism*
- Protein Multimerization/physiology*
- Protein Structure, Tertiary
- Signal Transduction/physiology*
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 25656526 Full text @ Biopolymers
Citation
Barton, R., Driscoll, A., Flores, S., Mudbhari, D., Collins, T., Iovine, M.K., Berger, B.W. (2015) Cysteines in the neuropilin-2 MAM domain modulate receptor homooligomerization and signal transduction. Biopolymers. 104(4):371-8.
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. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping