FHOD-1/profilin-mediated actin assembly protects sarcomeres against contraction-induced deformation in C. elegans .

Autor:	Kimmich MJ; Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, NY 13210., Sundaramurthy S; Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, NY 13210., Geary MA; Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, NY 13210., Lesanpezeshki L; Department of Chemical Engineering, Texas Tech University, Lubbock, TX 79409., Yingling CV; Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, NY 13210., Vanapalli SA; Department of Chemical Engineering, Texas Tech University, Lubbock, TX 79409., Littlefield RS; Biology Department, University of South Alabama, Mobile, AL 36688., Pruyne D; Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, NY 13210.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Apr 03. Date of Electronic Publication: 2024 Apr 03.
DOI:	10.1101/2024.02.29.582848
Abstrakt:	Formin HOmology Domain 2-containing (FHOD) proteins are a subfamily of actin-organizing formins important for striated muscle development in many animals. We showed previously that absence of the sole FHOD protein, FHOD-1, from C. elegans results in thin body-wall muscles with misshapen dense bodies that serve as sarcomere Z-lines. We demonstrate here that actin polymerization by FHOD-1 is required for its function in muscle development, and that FHOD-1 cooperates with profilin PFN-3 for dense body morphogenesis, and profilins PFN-2 and PFN-3 to promote body-wall muscle growth. We further demonstrate dense bodies in fhod-1 and pfn-3 mutants are less stable than in wild type animals, having a higher proportion of dynamic protein, and becoming distorted by prolonged muscle contraction. We also observe accumulation of actin depolymerization factor/cofilin homolog UNC-60B in body-wall muscle of these mutants. Such accumulations may indicate targeted disassembly of thin filaments dislodged from unstable dense bodies, and may account for the abnormally slow growth and reduced strength of body-wall muscle in fhod-1 mutants. Overall, these results show the importance of FHOD protein-mediated actin assembly to forming stable sarcomere Z-lines, and identify profilin as a new contributor to FHOD activity in striated muscle development. Competing Interests: Competing interests: S.A.V. is a co-founder of NemaLife, Inc., which has licensed the microfluidic technology NemaFlex for commercialization.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu