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J Physiol Volume 572, Number 3, 659-676, May 1, 2006 DOI: 10.1113/jphysiol.2006.106518
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Cellular

Dynamic association between {alpha}-actinin and ß-integrin regulates contraction of canine tracheal smooth muscle

Wenwu Zhang1 and Susan J. Gunst1

1 Department of Cellular and Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202, USA

The adhesion junctions of smooth muscle cells may be dynamically regulated during smooth muscle contraction, and this dynamic regulation may be important for the development of active tension. In the present study, the role of {alpha}-actinin during smooth muscle contraction was evaluated in tracheal smooth muscle tissues and freshly dissociated cells. Stimulation with acetylcholine (ACh) increased the localization of {alpha}-actinin at the membrane of freshly dissociated smooth muscle cells, and increased the amount of ß1 integrin that coprecipitated with {alpha}-actinin from muscle tissue homogenates. GFP-{alpha}-actinin fusion proteins were expressed in muscle tissues and visualized in live freshly dissociated cells. GFP-{alpha}-actinin translocated to the membrane within seconds of stimulation of the cells with ACh. Expression of the integrin-binding rod domain of {alpha}-actinin in smooth muscle tissues depressed active contraction in response to ACh. Expression of the {alpha}-actinin rod domain also inhibited the translocation of endogenous {alpha}-actinin to the membrane, and inhibited the association of endogenous {alpha}-actinin with ß1-integrin in {alpha}-actinin immunoprecipitates from tissue extracts. However, the expression of {alpha}-actinin rod domain peptides did not inhibit increases in myosin light chain phosphorylation or actin polymerization in response to stimulation with ACh. Results suggest that contractile stimulation of smooth muscle causes the rapid recruitment of {alpha}-actinin to ß-integrin complexes at the membrane, and that the recruitment of {alpha}-actinin to integrin complexes is necessary for active tension development in smooth muscle.

(Received 31 January 2006; accepted after revision 27 February 2006; first published online 2 March 2006)
Corresponding author S. J. Gunst: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, MS313 Indianapolis, IN 46202, USA. Email: sgunst{at}iupui.edu




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