Details

Autor(en) / Beteiligte

• Most, Patrick
• Remppis, Andrew
• Weber, Cornelia
• Bernotat, Juliane
• Ehlermann, Philipp
• Pleger, Sven T.
• Kirsch, Wolfgang
• Weber, Martin
• Uttenweiler, Dietmar
• Smith, Godfrey L.
• Katus, Hugo A.
• Fink, Rainer H.A.

Titel

The C Terminus (Amino Acids 75–94) and the Linker Region (Amino Acids 42–54) of the Ca2+-binding Protein S100A1 Differentially Enhance Sarcoplasmic Ca2+ Release in Murine Skinned Skeletal Muscle Fibers

Ist Teil von

• The Journal of biological chemistry, 2003-07, Vol.278 (29), p.26356-26364

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2003

Link zum Volltext

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• S100A1, a Ca2+-binding protein of the EF-hand type, is most highly expressed in striated muscle and has previously been shown to interact with the skeletal muscle sarcoplasmic reticulum (SR) Ca2+ release channel/ryanodine receptor (RyR1) isoform. However, it was unclear whether S100A1/RyR1 interaction could modulate SR Ca2+ handling and contractile properties in skeletal muscle fibers. Since S100A1 protein is differentially expressed in fast- and slow-twitch skeletal muscle, we used saponin-skinned murine Musculus extensor digitorum longus (EDL) and Musculus soleus (Soleus) fibers to assess the impact of S100A1 protein on SR Ca2+ release and isometric twitch force in functionally intact permeabilized muscle fibers. S100A1 equally enhanced caffeine-induced SR Ca2+ release and Ca2+-induced isometric force transients in both muscle preparations in a dose-dependent manner. Introducing a synthetic S100A1 peptide model (devoid of EF-hand Ca2+-binding sites) allowed identification of the S100A1 C terminus (amino acids 75–94) and hinge region (amino acids 42–54) to differentially enhance SR Ca2+ release with a nearly 3-fold higher activity of the C terminus. These effects were exclusively based on enhanced SR Ca2+ release as S100A1 influenced neither SR Ca2+ uptake nor myofilament Ca2+ sensitivity/cooperativity in our experimental setting. In conclusion, our study shows for the first time that S100A1 augments contractile performance both of fast- and slow-twitch skeletal muscle fibers based on enhanced SR Ca2+ efflux at least mediated by the C terminus of S100A1 protein. Thus, our data suggest that S100A1 may serve as an endogenous enhancer of SR Ca2+ release and might therefore be of physiological relevance in the process of excitation-contraction coupling in skeletal muscle.