© The Rockefeller University Press,
0021-9525/1997//1583 $5.00
The Journal of Cell Biology, Volume 139, Number 6,
, 1997 1583-1595
Muscle β1D Integrin Reinforces the Cytoskeleton–Matrix Link: Modulation of Integrin Adhesive Function by Alternative Splicing
Alexey M. Belkin*,
S. Francesco Retta
,
,
Olga Y. Pletjushkina
,
Fiorella Balzac
,
Lorenzo Silengo
,
Reinhard Fassler||,
Victor E. Koteliansky¶,
Keith Burridge*, and
Guido Tarone
,**
* Department of Cell Biology and Anatomy, University of North Carolina at Chapel Hill, North Carolina 27599;
Department of Biology, Genetics and Medical Chemistry, University of Torino, 10126 Torino, Italy;
Belozersky Institute of Physico-Chemical Biology, Moscow State University, 117311 Moscow, Russia; || Max-Planck-Institute for Biochemistry, Martinsried D-82152, Germany; ¶ Biogen Inc., Cambridge, Massachusetts 02142; ** Department of Psychology, University of Rome, Italy; and 
Institute of Biology, University of Palermo, 90133 Palermo, Italy
Expression of muscle-specific β1D integrin with an alternatively spliced cytoplasmic domain in CHO and GD25, β1 integrin-minus cells leads to their phenotypic conversion. β1D-transfected nonmuscle cells display rounded morphology, lack of pseudopodial activity, retarded spreading, reduced migration, and significantly enhanced contractility compared with their β1A-expressing counterparts. The transfected β1D is targeted to focal adhesions and efficiently displaces the endogenous β1A and
vβ3 integrins from the sites of cell–matrix contact. This displacement is observed on several types of extracellular matrix substrata and leads to elevated stability of focal adhesions in β1D transfectants. Whereas a significant part of cellular β1A integrin is extractable in digitonin, the majority of the transfected β1D is digitonin-insoluble and is strongly associated with the detergent-insoluble cytoskeleton. Increased interaction of β1D integrin with the actin cytoskeleton is consistent with and might be mediated by its enhanced binding to talin. In contrast, β1A interacts more strongly with
-actinin, than β1D. Inside-out driven activation of the β1D ectodomain increases ligand binding and fibronectin matrix assembly by β1D transfectants. Phenotypic effects of β1D integrin expression in nonmuscle cells are due to its enhanced interactions with both cytoskeletal and extracellular ligands. They parallel the transitions that muscle cells undergo during differentiation. Modulation of β1 integrin adhesive function by alternative splicing serves as a physiological mechanism reinforcing the cytoskeleton– matrix link in muscle cells. This reflects the major role for β1D integrin in muscle, where extremely stable association is required for contraction.
Address all correspondence to A.M. Belkin, Department of Biochemistry, American Red Cross, 15601 Crabbs Branch Way, Rockville, MD 20855. Tel.: (301) 738-0725. Fax: (301) 738-0794. E-mail: Belkina{at}usa.redcross.org

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-
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[Full Text]
-
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[Full Text]
-
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[Full Text]
-
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(2000). Regulation of mRNA and Protein Levels of {beta}1 Integrin Variants in Human Prostate Carcinoma. Am. J. Pathol.
157: 1727-1734
[Abstract]
[Full Text]
-
Fornaro, M., Steger, C. A., Bennett, A. M., Wu, J. J., Languino, L. R.
(2000). Differential Role of beta 1C and beta 1A Integrin Cytoplasmic Variants in Modulating Focal Adhesion Kinase, Protein Kinase B/AKT, and Ras/Mitogen-activated Protein Kinase Pathways. Mol. Biol. Cell
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[Abstract]
[Full Text]
-
Akimov, S. S., Krylov, D., Fleischman, L. F., Belkin, A. M.
(2000). Tissue Transglutaminase Is an Integrin-Binding Adhesion Coreceptor for Fibronectin. JCB
148: 825-838
[Abstract]
[Full Text]
-
Zent, R., Fenczik, C. A., Calderwood, D. A., Liu, S., Dellos, M., Ginsberg, M. H.
(2000). Class- and Splice Variant-specific Association of CD98 with Integrin beta Cytoplasmic Domains. J. Biol. Chem.
275: 5059-5064
[Abstract]
[Full Text]
-
Brancaccio, M., Guazzone, S., Menini, N., Sibona, E., Hirsch, E., De Andrea, M., Rocchi, M., Altruda, F., Tarone, G., Silengo, L.
(1999). Melusin Is a New Muscle-specific Interactor for beta 1 Integrin Cytoplasmic Domain. J. Biol. Chem.
274: 29282-29288
[Abstract]
[Full Text]
-
Saher, G., Hildt, E.
(1999). Activation of c-Raf-1 Kinase Signal Transduction Pathway in alpha 7 Integrin-deficient Mice. J. Biol. Chem.
274: 27651-27657
[Abstract]
[Full Text]
-
Hocking, D. C., Sottile, J., Reho, T., Fassler, R., McKeown-Longo, P. J.
(1999). Inhibition of Fibronectin Matrix Assembly by the Heparin-binding Domain of Vitronectin. J. Biol. Chem.
274: 27257-27264
[Abstract]
[Full Text]
-
Svineng, G, Johansson, S
(1999). Integrin subunits (beta)1C-1 and (beta)1C-2 expressed in GD25T cells are retained and degraded intracellularly rather than localised to the cell surface. J. Cell Sci.
112: 4751-4761
[Abstract]
-
Ra, H., Picart, C, Feng, H, Sweeney, H., Discher, D.
(1999). Muscle cell peeling from micropatterned collagen: direct probing of focal and molecular properties of matrix adhesion. J. Cell Sci.
112: 1425-1436
[Abstract]
-
Mastrangelo, A., Homan, S., Humphries, M., LaFlamme, S.
(1999). Amino acid motifs required for isolated beta cytoplasmic domains to regulate 'in trans' beta1 integrin conformation and function in cell attachment. J. Cell Sci.
112: 217-229
[Abstract]
-
Fornaro, M., Manzotti, M., Tallini, G., Slear, A. E., Bosari, S., Ruoslahti, E., Languino, L. R.
(1998). ß1C Integrin in Epithelial Cells Correlates with a Nonproliferative Phenotype : Forced Expression of ß1C Inhibits ProstateEpithelial Cell Proliferation. Am. J. Pathol.
153: 1079-1087
[Abstract]
[Full Text]
-
Ross, R. S., Pham, C., Shai, S.-Y., Goldhaber, J. I., Fenczik, C., Glembotski, C. C., Ginsberg, M. H., Loftus, J. C.
(1998). ß1 Integrins Participate in the Hypertrophic Response of Rat Ventricular Myocytes. Circ. Res.
82: 1160-1172
[Abstract]
[Full Text]
-
Belkin, A. M., Retta, S. F.
(1998). beta 1D Integrin Inhibits Cell Cycle Progression in Normal Myoblasts and Fibroblasts. J. Biol. Chem.
273: 15234-15240
[Abstract]
[Full Text]
-
Sakai, T., Zhang, Q., Fassler, R., Mosher, D. F.
(1998). Modulation of {beta}1A Integrin Functions by Tyrosine Residues in the {beta}1 Cytoplasmic Domain. JCB
141: 527-538
[Abstract]
[Full Text]
-
Yan, B., Calderwood, D. A., Yaspan, B., Ginsberg, M. H.
(2001). Calpain Cleavage Promotes Talin Binding to the beta 3 Integrin Cytoplasmic Domain. J. Biol. Chem.
276: 28164-28170
[Abstract]
[Full Text]
-
van der Flier, A., Kuikman, I., Kramer, D., Geerts, D., Kreft, M., Takafuta, T., Shapiro, S. S., Sonnenberg, A.
(2002). Different splice variants of filamin-B affect myogenesis, subcellular distribution, and determine binding to integrin {beta} subunits. JCB
156: 361-376
[Abstract]
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(2002). Serum response factor is crucial for actin cytoskeletal organization and focal adhesion assembly in embryonic stem cells. JCB
156: 737-750
[Abstract]
[Full Text]
-
Degani, S., Balzac, F., Brancaccio, M., Guazzone, S., Retta, S. F., Silengo, L., Eva, A., Tarone, G.
(2002). The integrin cytoplasmic domain-associated protein ICAP-1 binds and regulates Rho family GTPases during cell spreading. JCB
156: 377-388
[Abstract]
[Full Text]