title: SRP-35, a newly identified protein of the skeletal muscle sarcoplasmic reticulum, is a retinol dehydrogenase.
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.
authors: Department of Anaesthesia, Basel University Hospital, Hebelstrasse 20, 4031 Basel, Switzerland.
authors: Susan
authors: S
authors: Treves
authors: Raphael
authors: R
authors: Thurnheer
authors: Barbara
authors: B
authors: Mosca
authors: Mirko
authors: M
authors: Vukcevic
authors: Leda
authors: L
authors: Bergamelli
authors: Rebecca
authors: R
authors: Voltan
authors: Vitus
authors: V
authors: Oberhauser
authors: Michel
authors: M
authors: Ronjat
authors: Laszlo
authors: L
authors: Csernoch
authors: Peter
authors: P
authors: Szentesi
authors: Francesco
authors: F
authors: Zorzato
mesh_terms: D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009124:Muscle Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D009243:NAD; D000429:Alcohol Oxidoreductases; C113992:trans-retinol dehydrogenase; D002118:Calcium