Peripheral thickening of the sarcomeres and pointed end elongation of the thin filaments are both promoted by SALS and its formin interaction partners

Author:

Farkas DávidORCID,Szikora Szilárd,Jijumon A. S.ORCID,Polgár Tamás F.ORCID,Patai Roland,Tóth Mónika ÁgnesORCID,Bugyi BeátaORCID,Gajdos TamásORCID,Bíró PéterORCID,Novák TiborORCID,Erdélyi MiklósORCID,Mihály JózsefORCID

Abstract

During striated muscle development the first periodically repeated units appear in the premyofibrils, consisting of immature sarcomeres that must undergo a substantial growth both in length and width, to reach their final size. Here we report that, beyond its well established role in sarcomere elongation, the Sarcomere length short (SALS) protein is involved in Z-disc formation and peripheral growth of the sarcomeres. Our protein localization data and loss-of-function studies in the Drosophila indirect flight muscle strongly suggest that radial growth of the sarcomeres is initiated at the Z-disc. As to thin filament elongation, we used a powerful nanoscopy approach to reveal that SALS is subject to a major conformational change during sarcomere development, which might be critical to stop pointed end elongation in the adult muscles. In addition, we demonstrate that the roles of SALS in sarcomere elongation and radial growth are both dependent on formin type of actin assembly factors. Unexpectedly, when SALS is present in excess amounts, it promotes the formation of actin aggregates highly resembling the ones described in nemaline myopathy patients. Collectively, these findings helped to shed light on the complex mechanisms of SALS during the coordinated elongation and thickening of the sarcomeres, and resulted in the discovery of a potential nemaline myopathy model, suitable for the identification of genetic and small molecule inhibitors.

Funder

Hungarian Science Foundation

National Research, Development and Innovation Office

Nemzeti Kutatási, Fejlesztési és Innovaciós Alap

Hungarian Academy of Sciences

Ministry for Culture and Innovation

University of Pécs, Medical School

Publisher

Public Library of Science (PLoS)

Subject

Cancer Research,Genetics (clinical),Genetics,Molecular Biology,Ecology, Evolution, Behavior and Systematics

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