Myosins and pathology: genetics and biology.
This article summarizes current knowledge on the genetics and possible molecular mechanisms of Human pathologies resulted from mutations within the genes encoding several myosin isoforms. Mutations within the genes encoding some myosin isoforms have been found to be responsible for blindness (myosins III and VIIA), deafness (myosins I, IIA, IIIA, VI, VIIA and XV) and familial hypertrophic cardiomyopathy (beta cardiac myosin heavy chain and both the regulatory and essential light chains). Myosin III localizes predominantly to photoreceptor cells and is proved to be engaged in the vision process in Drosophila. In the inner ear, myosin I is postulated to play a role as an adaptive motor in the tip links of stereocilia of hair cells, myosin IIA seems to be responsible for stabilizing the contacts between adjacent inner ear hair cells, myosin VI plays a role as an intracellular motor transporting membrane structures within the hair cells while myosin VIIA most probably participates in forming links between neighbouring stereocilia and myosin XV probably stabilizes the stereocilia structure. About 30% of patients with familial hypertrophic cardiomyopathy have mutations within the genes encoding the beta cardiac myosin heavy chain and both light chains that are grouped within the regions of myosin head crucial for its functions. The alterations lead to the destabilization of sarcomeres and to a decrease of the myosin ATPase activity and its ability to move actin filaments.
Redowicz
Maria Jolanta
MJ
Department of Muscle Biochemistry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, L Pasteura 3, 02-093 Warszawa, Poland. jolanta@nencki.gov.pl
D000818:Animals; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics / Q000378:metabolism; D003638:Deafness / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009218:Myosins / Q000235:genetics* / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D014785:Vision, Ocular / Q000502:physiology
D020033:Protein Isoforms; D009218:Myosins