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Synaptic scaffolding molecule binds to and regulates vasoactive intestinal polypeptide type-1 receptor in epithelial cells.

Authors
 HEON YUNG GEE  ;  YOUNG WOONG KIM  ;  MIN JAE JO  ;  WAN NAMKUNG  ;  JOO YOUNG KIM  ;  HYUN WOO PARK  ;  KYUNG SIK KIM  ;  HOGUEN KIM  ;  AKEMICHI BABA  ;  JINHEE YANG  ;  EUNJOON KIM  ;  KYUNG HWAN KIM  ;  MIN GOO LEE 
Citation
 GASTROENTEROLOGY, Vol.137(2) : 607-617.e4, 2009 
Journal Title
 GASTROENTEROLOGY 
ISSN
 0016-5085 
Issue Date
2009
MeSH
Analysis of Variance ; Carrier Proteins ; Cell Communication/genetics ; Cell Communication/physiology ; Cells, Cultured ; Epithelial Cells/metabolism* ; Epithelial Cells/physiology ; Gene Expression Regulation ; Humans ; Immunoblotting ; Immunohistochemistry ; Probability ; Protein Binding/genetics ; Protein Binding/physiology* ; Receptors, Vasoactive Intestinal Polypeptide, Type I/genetics ; Receptors, Vasoactive Intestinal Polypeptide, Type I/metabolism* ; Signal Transduction/genetics ; Two-Hybrid System Techniques
Abstract
BACKGROUND & AIMS: Vasoactive intestinal polypeptide (VIP) is a principal regulator of fluid and electrolyte secretion in the gastrointestinal system. The VIP type-1 receptor (VPAC1), a class II G-protein-coupled receptor, contains a putative C-terminal PDZ-binding motif. A yeast 2-hybrid screen indicated that the C-terminus of VPAC1 bound to the PDZ domain of synaptic scaffolding molecule (S-SCAM, also known as membrane-associated guanylate kinase inverted-2 [MAGI-2]). We analyzed the association between S-SCAM and VPAC1. METHODS: The biochemical properties and physiologic significance of the interaction between VPAC1 and S-SCAM were examined in heterologous expression systems, T84 colonic epithelial cells, and human pancreas and colon tissues using an integrated molecular and physiologic approach. RESULTS: The physical interaction between VPAC1 and S-SCAM was confirmed by immunoprecipitation in HEK 293 mammalian cells and human pancreatic and colonic tissues. Immunocytochemical analysis indicated that S-SCAM recruited VPAC1 to the junctional area near the apical end of the lateral membrane in T84 cells. Several lines of evidence revealed that S-SCAM inhibits VPAC1 activation. Overexpression of S-SCAM inhibited VPAC1-mediated cAMP production and agonist-induced VPAC1 internalization in HEK 293 and HeLa cells. In addition, S-SCAM decreased the VPAC1-mediated current through the cystic fibrosis transmembrane conductance regulator in Xenopus oocytes, especially at low concentrations of VIP. Importantly, loss of S-SCAM increased VIP-induced short-circuit currents in T84 monolayers, which endogenously express VPAC1 and S-SCAM. CONCLUSIONS: S-SCAM/MAGI-2 interacts with and regulates VPAC1 intracellular localization in epithelial cells and inhibits VPAC1 agonist-induced activation and internalization.
Full Text
http://www.sciencedirect.com/science/article/pii/S0016508509001693
DOI
10.1053/j.gastro.2009.01.065
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sik(김경식) ORCID logo https://orcid.org/0000-0001-9498-284X
Kim, Kyung Hwan(김경환)
Kim, Joo Young(김주영) ORCID logo https://orcid.org/0000-0003-2623-1491
Kim, Ho Keun(김호근)
Park, Hyun Woo(박현우)
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
Gee, Heon Yung(지헌영) ORCID logo https://orcid.org/0000-0002-8741-6177
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/104213
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