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 journalArticle

7 Citations (Scopus)

Abstract

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
Volume10
Issue number9
DOIs
StatePublished - Sep 1 2015

Fingerprint

sequence homology
Muscle
skeletal muscle
Skeletal Muscle
Muscles
muscles
myoblasts
mice
creatine kinase
Myoblasts
recycling
adenosinetriphosphatase
Creatine Kinase
Adenosine Triphosphatases
Recycling
muscular dystrophy
proteins
muscular diseases
cell aggregates
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Demonbreun, A. R., Swanson, K. E., Rossi, A. E., Deveaux, H. K., Earley, J. U., Allen, M. V., ... McNally, E. M. (2015). Eps 15 homology domain (EHD)-1 remodels transverse tubules in skeletal muscle. PloS one, 10(9), [e0136679]. https://doi.org/10.1371/journal.pone.0136679

Eps 15 homology domain (EHD)-1 remodels transverse tubules in skeletal muscle. / Demonbreun, Alexis R.; Swanson, Kaitlin E.; Rossi, Ann E.; Deveaux, H. Kieran; Earley, Judy U.; Allen, Madison V.; Arya, Priyanka; Bhattacharyya, Sohinee; Band, Hamid; Pytel, Peter; McNally, Elizabeth M.

In: PloS one, Vol. 10, No. 9, e0136679, 01.09.2015.

Research output: Contribution to journalArticle

Demonbreun, AR, Swanson, KE, Rossi, AE, Deveaux, HK, Earley, JU, Allen, MV, Arya, P, Bhattacharyya, S, Band, H, Pytel, P & McNally, EM 2015, 'Eps 15 homology domain (EHD)-1 remodels transverse tubules in skeletal muscle', PloS one, vol. 10, no. 9, e0136679. https://doi.org/10.1371/journal.pone.0136679
Demonbreun AR, Swanson KE, Rossi AE, Deveaux HK, Earley JU, Allen MV et al. Eps 15 homology domain (EHD)-1 remodels transverse tubules in skeletal muscle. PloS one. 2015 Sep 1;10(9). e0136679. https://doi.org/10.1371/journal.pone.0136679
Demonbreun, Alexis R. ; Swanson, Kaitlin E. ; Rossi, Ann E. ; Deveaux, H. Kieran ; Earley, Judy U. ; Allen, Madison V. ; Arya, Priyanka ; Bhattacharyya, Sohinee ; Band, Hamid ; Pytel, Peter ; McNally, Elizabeth M. / Eps 15 homology domain (EHD)-1 remodels transverse tubules in skeletal muscle. In: PloS one. 2015 ; Vol. 10, No. 9.
@article{b257f4cbbddd4bf3a932fe020b508a01,
title = "Eps 15 homology domain (EHD)-1 remodels transverse tubules in skeletal muscle",
abstract = "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.",
author = "Demonbreun, {Alexis R.} and Swanson, {Kaitlin E.} and Rossi, {Ann E.} and Deveaux, {H. Kieran} and Earley, {Judy U.} and Allen, {Madison V.} and Priyanka Arya and Sohinee Bhattacharyya and Hamid Band and Peter Pytel and McNally, {Elizabeth M.}",
year = "2015",
month = "9",
day = "1",
doi = "10.1371/journal.pone.0136679",
language = "English (US)",
volume = "10",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "9",

}

TY - JOUR

T1 - Eps 15 homology domain (EHD)-1 remodels transverse tubules in skeletal muscle

AU - Demonbreun, Alexis R.

AU - Swanson, Kaitlin E.

AU - Rossi, Ann E.

AU - Deveaux, H. Kieran

AU - Earley, Judy U.

AU - Allen, Madison V.

AU - Arya, Priyanka

AU - Bhattacharyya, Sohinee

AU - Band, Hamid

AU - Pytel, Peter

AU - McNally, Elizabeth M.

PY - 2015/9/1

Y1 - 2015/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84943311596&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84943311596&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0136679

DO - 10.1371/journal.pone.0136679

M3 - Article

C2 - 26325203

AN - SCOPUS:84943311596

VL - 10

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 9

M1 - e0136679

ER -