title: Dynamic association between alpha-actinin and beta-integrin regulates contraction of canine tracheal smooth muscle.
abstract: 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 beta1 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 beta1-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 beta-integrin complexes at the membrane, and that the recruitment of alpha-actinin to integrin complexes is necessary for active tension development in smooth muscle.
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202, USA.
authors.forename: Wenwu
authors.initials: W
authors.lastname: Zhang
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Gunst
mesh_terms: D000185:Actinin / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000502:physiology / Q000648:ultrastructure; D004285:Dogs; D005109:Extracellular Matrix / Q000502:physiology / Q000648:ultrastructure; D005246:Feedback / Q000502:physiology; D006801:Humans; D039641:Integrin beta Chains / Q000378:metabolism*; D008168:Lung; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D013314:Stress, Mechanical; D014132:Trachea / Q000166:cytology / Q000502:physiology*
chemical_list: D039641:Integrin beta Chains; D000185:Actinin