The neonatal sarcoplasmic reticulum Ca2+-ATPase gives a clue to development and pathology in human muscles

J Muscle Res Cell Motil. 2015 Apr;36(2):195-203. doi: 10.1007/s10974-014-9403-z. Epub 2014 Dec 9.

Abstract

The sarcoplasmic/endoplasmic reticulum calcium ATPase 1 (SERCA1) has two muscle specific splice isoforms; SERCA1a in fast-type adult and SERCA1b in neonatal and regenerating skeletal muscles. At the protein level the only difference between these two isoforms is that SERCA1a has C-terminal glycine while SERCA1b has an octapeptide tail instead. This makes the generation of a SERCA1a specific antibody not feasible. The switch between the two isoforms is a hallmark of differentiation so we describe here a method based on the signal ratios of the SERCA1b specific and pan SERCA1 antibodies to estimate the SERCA1b/SERCA1a dominance on immunoblot of human muscles. Using this method we showed that unlike in mouse and rat, SERCA1b was only expressed in pre-matured infant leg and arm muscles; it was replaced by SERCA1a in more matured neonatal muscles and was completely absent in human foetal and neonatal diaphragms. Interestingly, only SERCA1a and no SERCA1b were detected in muscles of 7-12 years old boys with Duchenne, a degenerative-regenerative muscular dystrophy. However, in adult patients with myotonic dystrophy type 2 (DM2), the SERCA1b dominated over SERCA1a. Thus the human SERCA1b has a different expression pattern from that of rodents and it is associated with DM2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alternative Splicing*
  • Animals
  • Child
  • Female
  • Gene Expression Regulation, Enzymologic*
  • Humans
  • Infant, Newborn
  • Isoenzymes / biosynthesis
  • Isoenzymes / genetics
  • Male
  • Mice
  • Muscle, Skeletal / enzymology*
  • Muscle, Skeletal / pathology
  • Muscular Dystrophy, Duchenne / enzymology*
  • Muscular Dystrophy, Duchenne / genetics
  • Muscular Dystrophy, Duchenne / pathology
  • Myotonic Dystrophy / enzymology*
  • Myotonic Dystrophy / genetics
  • Myotonic Dystrophy / pathology
  • Rats
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / biosynthesis*
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / genetics

Substances

  • Atp2a1 protein, rat
  • Isoenzymes
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • ATP2A1 protein, human