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Vol. 14, Issue 9, 3507-3518, September 2003

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The 1 Cytoplasmic Domain Regulates the Laminin-binding Specificity of the 7X1 Integrin

Ming-Guang Yeh ^*, Barry L. Ziober ^* , Baomei Liu ^*, Galina Lipkina ^*, Ioannis S. Vizirianakis ^* , and Randall H. Kramer ^*  ||

^* Department of Stomatology, University of California at San Francisco, San Francisco, CA 94143-0512; Department of Anatomy, University of California at San Francisco, San Francisco, CA 94143-0512

Submitted December 15, 2002; Revised May 16, 2003; Accepted May 18, 2003
Monitoring Editor: Jean Schwarzbauer

During muscle development, the laminin-specific 7 integrin is alternatively spliced in the putative ligand-binding domain to yield either the 7X1 or the 7X2 variant. The relative level of 7X1 and 7X2 is developmentally regulated. Similarly, the partner 1 integrin cytoplasmic domain is converted from the 1A to the 1D splice variant. To determine whether 1D modulates the activity of the 7 receptor, cells were transfected with 7X1 and 1D cDNA. 7X1 coupled with 1A failed to adhere to laminin-1, whereas cotransfectants expressing 7X1 and 1D showed strong adhesion. Interestingly, 7X1 complexed with 1A and 1D displayed the same level of poor adhesion to laminin-2/4 or strong adhesion to laminin-10/11. These findings indicate that 7 function is regulated not only by X1/X2 in its extracellular domain but also by 1 cytoplasmic splice variants. It is likely that expression of 1D alters 7X1 binding to laminin isoforms by a process related to ligand affinity modulation. Functional regulation of 71 by developmentally regulated splicing events may be important during myogenic differentiation and repair because the integrin mediates adhesion, motility, and cell survival.

Abbreviations used: DMSO, dimethyl sulfoxide; FACS, fluorescence-activated cell sorting; FITC, fluorescein isothiocyanate; mAb, monoclonal antibody; MTJ, myotendinous junction; NMJ, neuromuscular junction; pAb, polyclonal antibody; PCR, polymerase chain reaction.

Present addresses: Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, PA 19104

Present addresses: Laboratory of Pharmacology, Department of Pharmaceutical Sciences, Aristotle University of Thessaloniki, GR-54006, Thessaloniki, Greece.

^|| Corresponding author. E-mail address: rkramer{at}itsa.ucsf.edu.