Effects of mutant lamins on nucleo-cytoskeletal coupling in Drosophila models of LMNA muscular dystrophy

Nicholas M. Shaw; Jose L. Rios-Monterrosa; Gregory R. Fedorchak; Margaret R. Ketterer; Gary S. Coombs; Jan Lammerding; Lori L. Wallrath

doi:10.3389/fcell.2022.934586

Back

Effects of mutant lamins on nucleo-cytoskeletal coupling in Drosophila models of LMNA muscular dystrophy

Journal article

Open access

Peer reviewed

Effects of mutant lamins on nucleo-cytoskeletal coupling in Drosophila models of LMNA muscular dystrophy

Nicholas M. Shaw, Jose L. Rios-Monterrosa, Gregory R. Fedorchak, Margaret R. Ketterer, Gary S. Coombs, Jan Lammerding and Lori L. Wallrath

Frontiers in cell and developmental biology, Vol.10, 934586

08/01/2022

DOI: 10.3389/fcell.2022.934586

PMCID: PMC9471154

PMID: 36120560

Files and links (1)

url

https://doi.org/10.3389/fcell.2022.934586View

Published (Version of record) Open Access

Abstract

The nuclei of multinucleated skeletal muscles experience substantial external force during development and muscle contraction. Protection from such forces is partly provided by lamins, intermediate filaments that form a scaffold lining the inner nuclear membrane. Lamins play a myriad of roles, including maintenance of nuclear shape and stability, mediation of nuclear mechanoresponses, and nucleo-cytoskeletal coupling. Herein, we investigate how disease-causing mutant lamins alter myonuclear properties in response to mechanical force. This was accomplished via a novel application of a micropipette harpooning assay applied to larval body wall muscles of Drosophila models of lamin-associated muscular dystrophy. The assay enables the measurement of both nuclear deformability and intracellular force transmission between the cytoskeleton and nuclear interior in intact muscle fibers. Our studies revealed that specific mutant lamins increase nuclear deformability while other mutant lamins cause nucleo-cytoskeletal coupling defects, which were associated with loss of microtubular nuclear caging. We found that microtubule caging of the nucleus depended on Msp300, a KASH domain protein that is a component of the linker of nucleoskeleton and cytoskeleton (LINC) complex. Taken together, these findings identified residues in lamins required for connecting the nucleus to the cytoskeleton and suggest that not all muscle disease-causing mutant lamins produce similar defects in subcellular mechanics.

Drosophila

lamins

LINC complex

microtubules

muscular dystrophies

myonuclei

Details

Title: Subtitle: Effects of mutant lamins on nucleo-cytoskeletal coupling in Drosophila models of LMNA muscular dystrophy
Creators: Nicholas M. Shaw - Roy J. and Lucille A. Carver College of Medicine
Jose L. Rios-Monterrosa - University of Iowa
Gregory R. Fedorchak - Cornell University
Margaret R. Ketterer - University of Iowa
Gary S. Coombs - Biology Department, Waldorf University, Forest City, IA, United States
Jan Lammerding - Cornell University
Lori L. Wallrath - University of Iowa
Resource Type: Journal article
Publication Details: Frontiers in cell and developmental biology, Vol.10, 934586
DOI: 10.3389/fcell.2022.934586
PMID: 36120560
PMCID: PMC9471154
NLM abbreviation: Front Cell Dev Biol
ISSN: 2296-634X
eISSN: 2296-634X
Publisher: Frontiers Media S.A
Grant note: DOI: 10.13039/100005202, name: Muscular Dystrophy Association; DOI: 10.13039/100000002, name: National Institutes of Health National Science Foundation Volkswagen Foundation; DOI: 10.13039/100008893, name: University of Iowa Burroughs Wellcome Fund
Language: English
Date published: 08/01/2022
Academic Unit: Microbiology and Immunology; Biochemistry and Molecular Biology; University College Courses
Record Identifier: 9984293558902771

Metrics

26 Record Views

20 Times Cited - Web of Science