Roles of Nebulin Family Members in the Heart

Circ J. 2015;79(10):2081-7. doi: 10.1253/circj.CJ-15-0854. Epub 2015 Aug 31.

Abstract

The members of the nebulin protein family, including nebulin, nebulette, LASP-1, LASP-2, and N-RAP, contain various numbers of nebulin repeats and bind to actin, but are otherwise heterogeneous with regard to size, expression pattern, and function. This review focuses on the roles of nebulin family members in the heart. Nebulin is the largest member predominantly expressed in skeletal muscle, where it stretches along the thin filament. In heart, nebulin is detectable only at low levels and its absence has no apparent effects. Nebulette is similar in structure to the nebulin C-terminal Z-line region and specifically expressed in heart. Nebulette gene mutations have been identified in dilated cardiomyopathy patients and transgenic mice overexpressing nebulette mutants partially recapitulate the human pathology. In contrast, nebulette knockout mice show no functional phenotype, but exhibit Z-line widening. LASP-2 is an isoform of nebulette expressed in multiple tissues, including the heart. It is present in the Z-line and intercalated disc and able to bind and cross-link filamentous actin. LASP-1 is similar in structure to LASP-2, but expressed only in non-muscle tissue. N-RAP is present in myofibril precursors during myofibrillogenesis and thought to be involved in myofibril assembly, while it is localized at the intercalated disc in adult heart. Additional in vivo models are required to provide further insights into the functions of nebulin family members in the heart.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adult
  • Animals
  • Cardiomyopathy, Dilated / genetics
  • Cardiomyopathy, Dilated / metabolism*
  • Cardiomyopathy, Dilated / pathology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • LIM Domain Proteins / genetics
  • LIM Domain Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Mutation*
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Myofibrils / genetics
  • Myofibrils / metabolism*
  • Myofibrils / pathology

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cytoskeletal Proteins
  • Homeodomain Proteins
  • LASP1 protein, human
  • LIM Domain Proteins
  • Lasp1 protein, mouse
  • Muscle Proteins
  • NEBL protein, human
  • Nebl protein, mouse
  • nebulin

Supplementary concepts

  • Familial dilated cardiomyopathy