JCB logo
Accuri Cytometers
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 21 January 2002. doi:10.1083/jcb.200103037
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 1035K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by van der Flier, A.
Right arrow Articles by Sonnenberg, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by van der Flier, A.
Right arrow Articles by Sonnenberg, A.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*Protein
*UniGene
*Genetics Home Reference
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

© The Rockefeller University Press, 0021-9525/2002/1/361 $5.00
The Journal of Cell Biology, Volume 156, Number 2, January 21, 2002 361-376

Article

Different splice variants of filamin-B affect myogenesis, subcellular distribution, and determine binding to integrin ß subunits



Arjan van der Flier1, Ingrid Kuikman1, Duco Kramer1, Dirk Geerts1, Maaike Kreft1, Toshiro Takafuta2, Sandor S. Shapiro2 and Arnoud Sonnenberg1

1 Netherlands Cancer Institute, Division of Cell Biology, 1066 CX Amsterdams, Netherlands
2 Cardeza Foundation for Hematologic Research, Department of Medicine, Jefferson Medical College, Philadelphia, PA 19107

Address correspondence to Arnoud Sonnenberg, Division of Cell Biology, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands. Tel.: (31) 20-512-1942. Fax: (31) 20-512-1944. E-mail: asonn{at}nki.nl

Integrins connect the extracellular matrix with the cell interior, and transduce signals through interactions of their cytoplasmic tails with cytoskeletal and signaling proteins. Using the yeast two-hybrid system, we isolated a novel splice variant (filamin-Bvar-1) of the filamentous actin cross-linking protein, filamin-B, that interacts with the cytoplasmic domain of the integrin ß1A and ß1D subunits. RT-PCR analysis showed weak, but wide, expression of filamin-Bvar-1 and a similar splice variant of filamin-A (filamin-Avar-1) in human tissues. Furthermore, alternative splice variants of filamin-B and filamin-C, from which the flexible hinge-1 region is deleted ({Delta}H1), were induced during in vitro differentiation of C2C12 mouse myoblasts. We show that both filamin-Avar-1 and filamin-Bvar-1 bind more strongly than their wild-type isoforms to different integrin ß subunits. The mere presence of the high-affinity binding site for ß1A is not sufficient for targeting the filamin-Bvar-1 construct to focal contacts. Interestingly, the simultaneous deletion of the H1 region is required for the localization of filamin-B at the tips of actin stress fibers. When expressed in C2C12 cells, filamin-Bvar-1({Delta}H1) accelerates their differentiation into myotubes. Furthermore, filamin-B variants lacking the H1 region induce the formation of thinner myotubes than those in cells containing variants with this region. These findings suggest that specific combinations of filamin mRNA splicing events modulate the organization of the actin cytoskeleton and the binding affinity for integrins.

Key Words: filamin isoforms; alternative splicing; ß1D integrin; myogenesis; cytoskeleton


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents