TY - JOUR
T1 - The Integrin-Adhesome is Required to Maintain Muscle Structure, Mitochondrial ATP Production, and Movement Forces in Caenorhabditis Elegans
AU - Etheridge, Timothy
AU - Rahman, Md
AU - Gaffney, Christopher J
AU - Shaw, Debra
AU - Shepherd, Freya
AU - Magudia, Jignesh
AU - Solomon, Deepak E
AU - Milne, Thomas
AU - Blawzdziewicz, Jerzy
AU - Constantin-Teodosiu, Dumitru
AU - Greenhaff, Paul L
AU - Vanapalli, Siva
AU - Szewczyk, Nathaniel J
PY - 2015/4
Y1 - 2015/4
N2 - The integrin-adhesome network, which contains >150 proteins, is mechano-transducing and located at discreet positions along the cell-cell and cell-extracellular matrix interface. A small subset of the integrin-adhesome is known to maintain normal muscle morphology. However, the importance of the entire adhesome for muscle structure and function is unknown. We used RNA interference to knock down 113 putative Caenorhabditis elegans homologs constituting most of the mammalian adhesome and 48 proteins known to localize to attachment sites in C. elegans muscle. In both cases, we found >90% of components were required for normal muscle mitochondrial structure and/or proteostasis vs. empty vector controls. Approximately half of these, mainly proteins that physically interact with each other, were also required for normal sarcomere and/or adhesome structure. Next we confirmed that the dystrophy observed in adhesome mutants associates with impaired maximal mitochondrial ATP production (P < 0.0
AB - The integrin-adhesome network, which contains >150 proteins, is mechano-transducing and located at discreet positions along the cell-cell and cell-extracellular matrix interface. A small subset of the integrin-adhesome is known to maintain normal muscle morphology. However, the importance of the entire adhesome for muscle structure and function is unknown. We used RNA interference to knock down 113 putative Caenorhabditis elegans homologs constituting most of the mammalian adhesome and 48 proteins known to localize to attachment sites in C. elegans muscle. In both cases, we found >90% of components were required for normal muscle mitochondrial structure and/or proteostasis vs. empty vector controls. Approximately half of these, mainly proteins that physically interact with each other, were also required for normal sarcomere and/or adhesome structure. Next we confirmed that the dystrophy observed in adhesome mutants associates with impaired maximal mitochondrial ATP production (P < 0.0
U2 - 10.1096/fj.14-259119
DO - 10.1096/fj.14-259119
M3 - Article
SP - 1235
EP - 1246
JO - FASEB Journal
JF - FASEB Journal
ER -