Talin 1 and 2 are required for myoblast fusion, sarcomere assembly and the maintenance of myotendinous junctions
Author:
Conti Francesco J.1, Monkley Sue J.2, Wood Malcolm R.1, Critchley David R.2, Müller Ulrich1
Affiliation:
1. The Scripps Research Institute, Department of Cell Biology and Institute of Childhood and Neglected Diseases, La Jolla, CA 92037, USA. 2. University of Leicester, Department of Biochemistry, Leicester LE1 9HN,UK.
Abstract
Talin 1 and 2 connect integrins to the actin cytoskeleton and regulate the affinity of integrins for ligands. In skeletal muscle, talin 1 regulates the stability of myotendinous junctions (MTJs), but the function of talin 2 in skeletal muscle is not known. Here we show that MTJ integrity is affected in talin 2-deficient mice. Concomitant ablation of talin 1 and 2 leads to defects in myoblast fusion and sarcomere assembly, resembling defects in muscle lacking β1 integrins. Talin 1/2-deficient myoblasts express functionally active β1 integrins, suggesting that defects in muscle development are not primarily caused by defects in ligand binding, but rather by disruptions of the interaction of integrins with the cytoskeleton. Consistent with this finding, assembly of integrin adhesion complexes is perturbed in the remaining muscle fibers of talin 1/2-deficient mice. We conclude that talin 1 and 2 are crucial for skeletal muscle development, where they regulate myoblast fusion,sarcomere assembly and the maintenance of MTJs.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Reference62 articles.
1. Araya, R., Eckardt, D., Maxeiner, S., Kruger, O., Theis, M.,Willecke, K. and Saez, J. C. (2005). Expression of connexins during differentiation and regeneration of skeletal muscle: functional relevance of connexin43. J. Cell Sci.118, 27-37. 2. Balaban, N. Q., Schwarz, U. S., Riveline, D., Goichberg, P.,Tzur, G., Sabanay, I., Mahalu, D., Safran, S., Bershadsky, A., Addadi, L. et al. (2001). Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates. Nat. Cell Biol.3,466-472. 3. Bazzoni, G., Shih, D. T., Buck, C. A. and Hemler, M. E.(1995). Monoclonal antibody 9EG7 defines a novel beta 1 integrin epitope induced by soluble ligand and manganese, but inhibited by calcium. J. Biol. Chem.270,25570-25577. 4. Belkin, A. M., Zhidkova, N. I., Balzac, F., Altruda, F.,Tomatis, D., Maier, A., Tarone, G., Koteliansky, V. E. and Burridge, K.(1996). Beta 1D integrin displaces the beta 1A isoform in striated muscles: localization at junctional structures and signaling potential in nonmuscle cells. J. Cell Biol.132,211-226. 5. Belkin, A. M., Retta, S. F., Pletjushkina, O. Y., Balzac, F.,Silengo, L., Fassler, R., Koteliansky, V. E., Burridge, K. and Tarone, G.(1997). Muscle beta1D integrin reinforces the cytoskeleton-matrix link: modulation of integrin adhesive function by alternative splicing. J. Cell Biol.139,1583-1595.
Cited by
97 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|