Tropomodulins, cytoplasmic γ-actin, and small ankyrin 1.5 mechanically stabilize the sarcoplasmic reticulum and maintain myofibril alignment in skeletal muscle fibers

Allen

Almenar-Queralt

Bagnato

Bang

Belyantseva

Bennett

Borzok

Conley

Conover

Craig

Cunha

David S. Gokhin

Fischer

Fowler

Fritz-Six

Fukuzawa

Gallagher

Galustian

Gokhin

Gregorio

Hanft

Jaeger

Knight

Kontrogianni-Konstantopoulos

Lange

Littlefield

McKeown

Meyer

Miller

Milner

Mohler

Monti

Moyer

Nelson

Nowak

Otey

Otterbein

Pardo

Porter

Prins

Renley

Repasky

Rybakova

Shah

Sonnemann

Sung

Tonino

Velia M. Fowler

Vlahovich

Watakabe

Weber

Williams

Yamashiro

English

PubMed

The sarcoplasmic reticulum (SR) serves as the Ca2+ reservoir for muscle contraction. Tropomodulins (Tmods) cap filamentous actin (F-actin) pointed ends, bind tropomyosins (Tms), and regulate F-actin organization. In this paper, we use a genetic targeting approach to examine the effect of Tmod1 deletion on the organization of cytoplasmic γ-actin (γcyto-actin) in the SR of skeletal muscle. In wild-type muscle fibers, γcyto-actin and Tmod3 defined an SR microdomain that was distinct from another Z line–flanking SR microdomain containing Tmod1 and Tmod4. The γcyto-actin/Tmod3 microdomain contained an M line complex composed of small ankyrin 1.5 (sAnk1.5), γcyto-actin, Tmod3, Tm4, and Tm5NM1. Tmod1 deletion caused Tmod3 to leave its SR compartment, leading to mislocalization and destabilization of the Tmod3–γcyto-actin–sAnk1.5 complex. This was accompanied by SR morphological defects, impaired Ca2+ release, and an age-dependent increase in sarcomere misalignment. Thus, Tmod3 regulates SR-associated γcyto-actin architecture, mechanically stabilizes the SR via a novel cytoskeletal linkage to sAnk1.5, and maintains the alignment of adjacent myofibrils.</jats:p

Crossref

The Journal of Cell Biology

Cytoplasmic γ-actin and tropomodulin isoforms link to the sarcoplasmic reticulum in skeletal muscle fibers

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http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3135406

Cytoplasmic γ-actin and tropomodulin isoforms link to the sarcoplasmic reticulum in skeletal muscle fibers

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