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1D Integrin Reinforces the
Cytoskeleton-Matrix Link: Modulation of Integrin
Adhesive Function by Alternative Splicing
**
* Department of Cell Biology and Anatomy, University of North Carolina at Chapel Hill, North Carolina 27599; Expression of muscle-specific 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
1D integrin
with an alternatively spliced cytoplasmic domain in
CHO and GD25, 1 integrin-minus cells leads to their
phenotypic conversion. 1D-transfected nonmuscle cells display rounded morphology, lack of pseudopodial
activity, retarded spreading, reduced migration, and
significantly enhanced contractility compared with
their 1A-expressing counterparts. The transfected
1D is targeted to focal adhesions and efficiently displaces the endogenous 1A and 
v3 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 1D
transfectants. Whereas a significant part of cellular 1A
integrin is extractable in digitonin, the majority of the
transfected 1D is digitonin-insoluble and is strongly
associated with the detergent-insoluble cytoskeleton. Increased interaction of 1D integrin with the actin cytoskeleton is consistent with and might be mediated by
its enhanced binding to talin. In contrast, 1A interacts
more strongly with -actinin, than 1D. Inside-out
driven activation of the 1D ectodomain increases ligand binding and fibronectin matrix assembly by 1D
transfectants. Phenotypic effects of 1D 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 1 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 1D integrin in muscle, where extremely stable association is required for contraction.
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