Eps 15 homology domain (EHD)-1 remodels transverse tubules in skeletal muscle

Alexis R. Demonbreun, Kaitlin E. Swanson, Ann E. Rossi, H. Kieran Deveaux, Judy U. Earley, Madison V. Allen, Priyanka Arya, Sohinee Bhattacharyya, Hamid Band, Peter Pytel, Elizabeth M. McNally

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


We previously showed that Eps15 homology domain-containing 1 (EHD1) interacts with ferlin proteins to regulate endocytic recycling.Myoblasts from Ehd1-null mice were found to have defective recycling, myoblast fusion, and consequently smaller muscles. When expressed in C2C12 cells, an ATPase dead-EHD1 was found to interfere with BIN1/amphiphysin 2.We now extended those findings by examining Ehd1-heterozygous mice since these mice survive to maturity in normal Mendelian numbers and provide a ready source of mature muscle. We found that heterozygosity of EHD1 was sufficient to produce ectopic and excessive Ttubules, including large intracellular aggregates that contained BIN1. The disorganized Ttubule structures in Ehd1-heterozygous muscle were accompanied by marked elevation of the T-tubule-associated protein DHPR and reduction of the triad linker protein junctophilin 2, reflecting defective triads. Consistent with this, Ehd1-heterozygous muscle had reduced force production. Introduction of ATPase dead-EHD1 into mature muscle fibers was sufficient to induce ectopic T-tubule formation, seen as large BIN1 positive structures throughout the muscle. Ehd1-heterozygous mice were found to have strikingly elevated serum creatine kinase and smaller myofibers, but did not display findings of muscular dystrophy. These data indicate that EHD1 regulates the maintenance of T-tubules through its interaction with BIN1 and links T-tubules defects with elevated creatine kinase and myopathy.

Original languageEnglish (US)
Article numbere0136679
JournalPloS one
Issue number9
StatePublished - Sep 1 2015

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Eps 15 homology domain (EHD)-1 remodels transverse tubules in skeletal muscle'. Together they form a unique fingerprint.

Cite this