Cysteines in the neuropilin-2 MAM domain modulate receptor homooligomerization and signal transduction.
Biopolymers
; 104(4): 371-8, 2015 Jul.
Article
em En
| MEDLINE
| ID: mdl-25656526
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peixe-Zebra
/
Transdução de Sinais
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Proteínas de Peixe-Zebra
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Neuropilina-2
/
Multimerização Proteica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Biopolymers
Ano de publicação:
2015
Tipo de documento:
Article