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

Susan Treves, Raphael Thurnheer, Barbara Mosca, Mirko Vukcevic, Leda Bergamelli, Rebecca Voltan, Vitus Oberhauser, Michel Ronjat, Laszlo Csernoch, Peter Szentesi, Francesco Zorzato

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10 Citations (Scopus)

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 Ca 2+ released via RyR (ryanodine receptor) activation induced by KCl or 4-chlorom- 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 Ca 2+ release (i.e. muscle activity) to metabolism.

Original languageEnglish
Pages (from-to)731-741
Number of pages11
JournalBiochemical Journal
Volume441
Issue number2
DOIs
Publication statusPublished - Jan 15 2012

Keywords

  • Calcium release
  • Excitation-contraction coupling
  • Retinoic acid
  • Ryanodine receptor (RyR)
  • Skeletal muscle

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Treves, S., Thurnheer, R., Mosca, B., Vukcevic, M., Bergamelli, L., Voltan, R., Oberhauser, V., Ronjat, M., Csernoch, L., Szentesi, P., & Zorzato, F. (2012). SRP-35, a newly identified protein of the skeletal muscle sarcoplasmic reticulum, is a retinol dehydrogenase. Biochemical Journal, 441(2), 731-741. https://doi.org/10.1042/BJ20111457