Integrin-mediated adhesion maintains sarcomeric integrity.
Integrin-mediated adhesion to the ECM is essential for normal development of animal tissues. During muscle development, integrins provide the structural stability required to construct such a highly tensile, force generating tissue. Mutations that disrupt integrin-mediated adhesion in skeletal muscles give rise to a myopathy in humans and mice. To determine if this is due to defects in formation or defects in maintenance of muscle tissue, we used an inducible, targeted RNAi based approach to disrupt integrin-mediated adhesion in fully formed adult fly muscles. A decrease in integrin-mediated adhesion in adult muscles led to a progressive loss of muscle function due to a failure to maintain normal sarcomeric cytoarchitecture. This defect was due to a gradual, age dependent disorganization of the sarcomeric actin, Z-line, and M-line. Electron microscopic analysis showed that reduction in integrin-mediated adhesion resulted in detachment of actin filaments from the Z-lines, separation of the Z-lines from the membrane, and eventually to disintegration of the Z-lines. Our results show that integrin-mediated adhesion is essential for maintaining sarcomeric integrity and illustrate that the seemingly stable adhesive contacts underlying sarcomeric architecture are inherently dynamic.
Perkins
Alexander D
AD
Department of Cellular and Physiological Sciences, University of British Columbia, Life Science Institute, 2350 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3.
Ellis
Stephanie J
SJ
Asghari
Parisa
P
Shamsian
Arash
A
Moore
Edwin D W
ED
Tanentzapf
Guy
G
D000185:Actinin / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000375:Aging / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion; D002454:Cell Differentiation; D004331:Drosophila melanogaster / Q000166:cytology* / Q000201:enzymology / Q000254:growth & development / Q000648:ultrastructure; D005426:Flight, Animal; D055785:Gene Knockdown Techniques; D016023:Integrins / Q000378:metabolism*; D008954:Models, Biological; D009132:Muscles / Q000378:metabolism / Q000473:pathology; D009928:Organ Specificity; D010641:Phenotype; D012518:Sarcomeres / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D016608:Talin / Q000378:metabolism; D013997:Time Factors
D000199:Actins; D016023:Integrins; D016608:Talin; D000185:Actinin