Danesh H Sopariwala

The Ohio State University, Columbus, Ohio, United States

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Publications (5)41.81 Total impact

  • Meghna Pant, Danesh H Sopariwala, Naresh C Bal
    The Journal of Physiology 03/2014; 592(Pt 5):827-8. · 4.38 Impact Factor
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    ABSTRACT: SERCA pump activity is modulated by Phospholamban (PLB) and Sarcolipin (SLN) in cardiac and skeletal muscle. Recent data suggest that SLN could play a role in muscle thermogenesis by promoting uncoupling of the SERCA pump (Lee, A.G. (2002) Current opinion in structural biology 12(4):547-554 and Bal et al (2012) Nature Medicine 18(10):1575-1579) but the mechanistic details are unknown. To better define how binding of SLN to SERCA promotes uncoupling of SERCA, we compared SLN and SERCA1 interaction with that of PLB in detail. The homobifunctional cross-linker (1, 6-bismaleimidohexane (BMH)) was employed to detect dynamic protein interaction during the SERCA cycle. Our studies reveal that SLN differs significantly from PLB: 1) SLN primarily affects the V(max) of SERCA mediated Ca2+ uptake but not the pump affinity for Ca(2+) 2) SLN can bind to SERCA in the presence of high Ca(2+) but PLB can only interact to the ATP bound Ca(2+) free E2 state and 3) unlike PLB, SLN interacts with SERCA throughout the kinetic cycle and promotes uncoupling of the SERCA pump. Using SERCA transmembrane mutants we additionally show that PLB and SLN can bind to the same groove but interact with a different set of residues on SERCA. These data collectively suggest that SLN is functionally distinct from PLB; its ability to interact with SERCA in the presence of Ca(2+) causes uncoupling of the SERCA pump and increased heat production.
    Journal of Biological Chemistry 01/2013; · 4.60 Impact Factor
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    ABSTRACT: The role of skeletal muscle in nonshivering thermogenesis (NST) is not well understood. Here we show that sarcolipin (Sln), a newly identified regulator of the sarco/endoplasmic reticulum Ca(2+)-ATPase (Serca) pump, is necessary for muscle-based thermogenesis. When challenged to acute cold (4 °C), Sln(-/-) mice were not able to maintain their core body temperature (37 °C) and developed hypothermia. Surgical ablation of brown adipose tissue and functional knockdown of Ucp1 allowed us to highlight the role of muscle in NST. Overexpression of Sln in the Sln-null background fully restored muscle-based thermogenesis, suggesting that Sln is the basis for Serca-mediated heat production. We show that ryanodine receptor 1 (Ryr1)-mediated Ca(2+) leak is an important mechanism for Serca-activated heat generation. Here we present data to suggest that Sln can continue to interact with Serca in the presence of Ca(2+), which can promote uncoupling of the Serca pump and cause futile cycling. We further show that loss of Sln predisposes mice to diet-induced obesity, which suggests that Sln-mediated NST is recruited during metabolic overload. These data collectively suggest that SLN is an important mediator of muscle thermogenesis and whole-body energy metabolism.
    Nature medicine 09/2012; 18(10):1575-9. · 28.05 Impact Factor
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    ABSTRACT: CASQ (calsequestrin) is a Ca2+-buffering protein localized in the muscle SR (sarcoplasmic reticulum); however, it is unknown whether Ca2+ binding to CASQ2 is due to its location inside the SR rich in Ca2+ or due to its preference for Ca2+ over other ions. Therefore a major aim of the present study was to determine how CASQ2 selects Ca2+ over other metal ions by studying monomer folding and subsequent aggregation upon exposure to alkali (monovalent), alkaline earth (divalent) and transition (polyvalent) metals. We additionally investigated how CPVT (catecholaminergic polymorphic ventricular tachycardia) mutations affect CASQ2 structure and its molecular behaviour when exposed to different metal ions. Our results show that alkali and alkaline earth metals can initiate similar molecular compaction (folding), but only Ca2+ can promote CASQ2 to aggregate, suggesting that CASQ2 has a preferential binding to Ca2+ over all other metals. We additionally found that transition metals (having higher co-ordinated bonding ability than Ca2+) can also initiate folding and promote aggregation of CASQ2. These studies led us to suggest that folding and formation of higher-order structures depends on cationic properties such as co-ordinate bonding ability and ionic radius. Among the CPVT mutants studied, the L167H mutation disrupts the Ca2+-dependent folding and, when folding is achieved by Mn2+, L167H can undergo aggregation in a Ca2+-dependent manner. Interestingly, domain III mutants (D307H and P308L) lost their selectivity to Ca2+ and could be aggregated in the presence of Mg2+. In conclusion, these studies suggest that CPVT mutations modify CASQ2 behaviour, including folding, aggregation/polymerization and selectivity towards Ca2+.
    Biochemical Journal 01/2011; 435(2):391-9. · 4.78 Impact Factor
  • Mei Chi, Yingbi Zhou, Danesh Sopariwala, Muthu Periasamy
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    ABSTRACT: We previously showed that complete loss of smooth muscle myosin heavy chain isoform 2 (SM2) resulted in postnatal lethality, but in het mice a partial loss of SM2 (SM2(+/-)) was accompanied by down-regulation of SM1 with unaltered SM2:SM1 ratio. To determine whether a normal bladder function would be maintained throughout its lifespan, we aged WT and SM2(+/-) mice up to 18 months and analyzed a) SM2:SM1 ratio b) bladder smooth muscle structure and c) function in SM2(+/-) het mice. A notable finding was that ~50% of 15-18 months old male SM2(+/-) mice exhibited urinary retention in bladder with the distention of upper urethra. In SM2(+/-) mouse bladder with urinary retention, the SM2:SM1 ratio was decreased but not in SM2(+/-) mouse bladder that did not develop urinary retention. Interestingly in the distended bladder the expression levels of α-actin and tropomyosin remained unaltered despite a reduction in the number of myosin thick filaments. These distended bladders showed hypersensitivity to submaximal K(+) depolarization and M3-receptor stimulation, without a significant increase in myosin light chain phosphorylation. We therefore suggest that a partial loss of SM2 may predispose male mice to develop lower urinary tract obstruction during ageing. In addition our data suggest that bladder obstruction can cause a further reduction in SM2 expression and SM2:SM1 ratio, and a hyper-contractility of the bladder smooth muscle.
    Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi. 01/2011; 47(3-4):67-78.

Publication Stats

54 Citations
41.81 Total Impact Points


  • 2011–2014
    • The Ohio State University
      • Department of Physiology and Cell Biology
      Columbus, Ohio, United States