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PMID: 15361073 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

ADP-ribosylation of integrin alpha7 modulates the binding of integrin alpha7beta1 to laminin.

The Biochemical journal ·Vol. 385 ·No. Pt 1 ·2005-01-01 ·Pages 309-17

Zhao Z, Gruszczynska-Biegala J, Zolkiewska A

Abstract

The extracellular domain of integrin alpha7 is ADP-ribosylated by an arginine-specific ecto-ADP-ribosyltransferase after adding exogenous NAD+ to intact C2C12 skeletal muscle cells. The effect of ADP-ribosylation on the structure or function of integrin alpha7beta1 has not been explored. In the present study, we show that ADP-ribosylation of integrin alpha7 takes place exclusively in differentiated myotubes and that this post-translational modification modulates the affinity of alpha7beta1 dimer for its ligand, laminin. ADP-ribosylation in the 37-kDa 'stalk' region of alpha7 that takes place at micromolar NAD+ concentrations increases the binding of the alpha7beta1 dimer to laminin. Increased in vitro binding of integrin alpha7beta1 to laminin after ADP-ribosylation of the 37-kDa fragment of alpha7 requires the presence of Mn2+ and it is not observed in the presence of Mg2+. In contrast, ADP-ribosylation of the 63-kDa N-terminal region comprising the ligand-binding site of alpha7 that occurs at approx. 100 microM NAD+ inhibits the binding of integrin alpha7beta1 to laminin. Furthermore, incubation of C2C12 myotubes with NAD+ increases the expression of an epitope on integrin beta1 subunit recognized by monoclonal antibody 9EG7. We discuss our results based on the current models of integrin activation. We also hypothesize that ADP-ribosylation may represent a mechanism of regulation of integrin alpha7beta1 function in myofibres in vivo when the continuity of the membrane is compromised and NAD+ is available as a substrate for ecto-ADP-ribosylation.

MeSH Terms
Adenosine Diphosphate Ribose/metabolism Animals Antigens, CD/chemistry,metabolism Cations, Divalent/pharmacology Cell Differentiation Cell Line Cells, Cultured Integrin alpha Chains/chemistry,metabolism Integrins/metabolism Laminin/metabolism Magnesium/pharmacology Manganese/pharmacology Mice NAD/pharmacology Protein Binding/drug effects Protein Conformation/drug effects
Chemicals
Antigens, CD Cations, Divalent Integrin alpha Chains Integrins Laminin integrin alpha7 NAD Adenosine Diphosphate Ribose Manganese Magnesium integrin alpha7beta1
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Zhao Zhefeng
Department of Biochemistry, Kansas State University, 104 Willard Hall, Manhattan, KS 66506, USA.
Gruszczynska-Biegala Joanna
Zolkiewska Anna
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
1470-8728
DOI
10.1042/BJ20040590
Published
2005-01-01
Pages
309-17
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1134699
Subset
IM
Grants
NCRR NIH HHS · P20 RR017708 · United States
NCRR NIH HHS · P20 RR17708 · United States
External Links
PubMed source DOI: 10.1042/BJ20040590 PMC Full Text View journal details
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