SRP-35, a newly identified protein of the skeletal muscle sarcoplasmic reticulum, is a retinol dehydrogenase

Biochem J. 2012 Jan 15;441(2):731-41. doi: 10.1042/BJ20111457.

Abstract

In the present study we provide evidence that SRP-35, a protein we identified in rabbit skeletal muscle sarcoplasmic reticulum, is an all-trans-retinol dehydrogenase. Analysis of the primary structure and tryptic digestion revealed that its N-terminus encompasses a short hydrophobic sequence bound to the sarcoplasmic reticulum membrane, whereas its C-terminal catalytic domain faces the myoplasm. SRP-35 is also expressed in liver and adipocytes, where it appears in the post-microsomal supernatant; however, in skeletal muscle, SRP-35 is enriched in the longitudinal sarcoplasmic reticulum. Sequence comparison predicts that SRP-35 is a short-chain dehydrogenase/reductase belonging to the DHRS7C [dehydrogenase/reductase (short-chain dehydrogenase/reductase family) member 7C] subfamily. Retinol is the substrate of SRP-35, since its transient overexpression leads to an increased production of all-trans-retinaldehyde. Transfection of C2C12 myotubes with a fusion protein encoding SRP-35-EYFP (enhanced yellow fluorescent protein) causes a decrease of the maximal Ca²⁺ released via RyR (ryanodine receptor) activation induced by KCl or 4-chloro-m-chresol. The latter result could be mimicked by the addition of retinoic acid to the C2C12 cell tissue culture medium, a treatment which caused a significant reduction of RyR1 expression. We propose that in skeletal muscle SRP-35 is involved in the generation of all-trans-retinaldehyde and may play an important role in the generation of intracellular signals linking Ca2+ release (i.e. muscle activity) to metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Oxidoreductases / metabolism*
  • Amino Acid Sequence
  • Animals
  • Calcium / metabolism
  • Cell Line
  • HEK293 Cells
  • Humans
  • Molecular Sequence Data
  • Muscle Contraction
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Proteins / chemistry
  • Muscle Proteins / isolation & purification
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / metabolism
  • NAD / metabolism
  • Rabbits
  • Ryanodine Receptor Calcium Release Channel / metabolism
  • Sarcoplasmic Reticulum / metabolism
  • Tissue Distribution

Substances

  • Muscle Proteins
  • Ryanodine Receptor Calcium Release Channel
  • NAD
  • Alcohol Oxidoreductases
  • trans-retinol dehydrogenase
  • Calcium