Flightin is essential for thick filament assembly and sarcomere stability in Drosophila flight muscles

被引:81
作者
Reedy, MC
Bullard, B
Vigoreaux, JO [1 ]
机构
[1] Univ Vermont, Dept Biol, Burlington, VT 05405 USA
[2] European Mol Biol Lab, D-69012 Heidelberg, Germany
[3] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA
关键词
flightin; myosin; thick filaments; insect flight muscle; muscle mutant;
D O I
10.1083/jcb.151.7.1483
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Flightin is a multiply phosphorylated, 20-kD myofibrillar protein found in Drosophila indirect flight muscles (IFM). Previous work suggests that flightin plays an essential, as yet undefined, role in normal sarcomere structure and contractile activity. Here we show that flightin is associated with thick filaments where it is likely to interact with the myosin rod. We have created a null mutation for flightin, fln(0), that results in loss of flight ability but has no effect on fecundity or viability. Electron microscopy comparing pupa and adult fln(0) LFM shows that sarcomeres, and thick and thin filaments in pupal IFM, are 25-30% longer than in wild type. fln(0) fibers are abnormally wavy, but sarcomere and myotendon structure in pupa are otherwise normal. Within the first 5 h of adult life and beginning of contractile activity, IFM fibers become disrupted as thick filaments and sarcomeres are variably shortened, and myofibrils are ruptured at the myotendon junction. Unusual empty pockets and granular material interrupt the filament lattice of adult fln(0) sarcomeres. Site-specific cleavage of myosin heavy chain occurs during this period. That myosin is cleaved in the absence of flightin is consistent with the immunolocalization of flightin on the thick filament and biochemical and genetic evidence suggesting it is associated with the myosin rod. Our results indicate that flightin is required for the establishment of normal thick filament length during late pupal development and thick filament stability in adult after initiation of contractile activity.
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页码:1483 / 1499
页数:17
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