Anatomy and Cell Biology

Masataka Kawai, PhD

Portrait

Professor of Anatomy and Cell Biology

Contact Information

Primary Office: 1-324 Bowen Science Building
Iowa City, IA 52242

Email: masataka-kawai@uiowa.edu

Education

BA, Science, University of Tokyo, Tokyo, Japan
Physiology Course, Marine Biological Laboratory, Woods Hole, MA
PhD, Biology, Princeton University, New Jersey

Post Doctoral, Columbia University, New York, New York

Education/Training Program Affiliations

Biosciences Graduate Program
Department of Anatomy and Cell Biology Graduate Program

Research Summary

Molecular mechanisms of contraction in striated muscles, and the mechanisms of hypertrophic and dilated cardiomyopathy (HCM, DCM).

To study the molecular mechanisms of contraction, it is essential that force can be measured, hence “skinned” single muscle fibers are used, in which the plasma membrane is chemically removed. To learn the function of individual amino acid residues in a contractile protein, it is necessary to replace it with a recombinant protein. We developed a system, in which the thin filament of cardiac fibers is selectively removed by gelsolin, and reconstituted by actin monomers, followed by regulatory proteins tropomyosin (Tpm) and troponin (Tn). Because this procedure does not require any adverse conditions (extreme ionic strength, pH, temperature, etc), the reproducibility of active tension is 104±3%; similarly, the reproducibility of other contractile parameters are excellent. This technique has numerous applications. One can study the actin-myosin interaction without Tpm/Tn; we found that Tpm/Tn increases force/cross-bridge by 50% indicating that the actin-Tpm interaction allosterically activates the actin-myosin interaction. This technique has also been used to study mutant proteins to establish the structure-function relationships. It was further used to learn molecular pathogenesis based on thin filament proteins (actin, Tpm, Tn) that are known to cause HCM and DCM in humans. The technique makes it possible to obtain information on early events of pathogenesis, ie, before complex signaling cascades ensue. In Tpm mutations that cause HCM, we found that tension at pCa 8 increases from 10% (WT) to 30% to cause diastolic problem, whereas in Tpm mutations that cause DCM, tension at pCa 8 and pCa 4.5 both decrease to cause systolic problem.

Complete publication: http://www.ncbi.nlm.nih.gov/pubmed/?term=Kawai+M

All Publications

Bai F, Caster H, Dawson J, Kawai M.  The immediate effect of HCM causing actin mutants E99K and A230V on actin-Tm-myosin interaction in thin-filament reconstituted myocardium.  J Mol Cell Cardiol.  2015. 79:123-132.
[Link]

Wang L, Sadayappan S, Kawai M.  Cardiac Myosin Binding Protein C Phosphorylation Affects Cross-bridge Cycle’s Elementary Steps in a Site-specific Manner.  Pros One.  2014. 
[Link]

Wang L, Ji X, Barefield D, Sadayappan S, Kawai M.  Phosphorylation of cMyBP-C affects contractile mechanisms in a site specific manner.  Biophys J.  2014. 106:1112-1122.
[Link]

Bai F, Caster H, Rubenstein P, Dawson J, Kawai M.  Using baculovirus/insect cell expressed recombinant actin to study the molecular pathogenesis of HCM caused by actin mutation A331P.  J Mol Cell Cardiol.  2014. 74:64-75.
[Link]

Wang L, Kawai M.  A re-interpretation of the rate of tension redevelopment (kTR) in active muscle. .  J Muscle Res Cell Motil.  2013. 34:407-415.
[PubMed]

Bai F, Wang L, Kawai M.  A study of tropomyosin’s role in cardiac function and disease using thin-filament reconstituted myocardium.  J Muscle Res Cell Motil.  2013. 34:295-310.
[PubMed]

Bai F, Caster H, Pinto J, Kawai M.  Analysis of the molecular pathogenesis of cardiomyopathy-causing cTnT mutants I79N, ΔE96, and ΔK210.  Biophys J.  2013. 104(9):1979-1988.

Wang L, Muthu P, Szczesna-Cordary D, Kawai M.  Characterizations of myosin essential light chain's N-terminal truncation mutant Δ43 in transgenic mouse papillary muscles by using tension transients in response to sinusoidal length alterations.  J Muscle Res Cell Motil.  2013. 34(9):93-105.
[PubMed]

Wang L, Muthu P, Szczesna-Cordary D, Kawai M.  Diversity and similarity of motor function and cross-bridge kinetics in papillary muscles of transgenic mice carrying myosin regulatory light chain mutations D166V and R58Q.  J Molec Cell Cardiol.  2013. 62(153-163).
[PubMed]

Iorga B, Wang L, Stehle R, Pfitzer G, Kawai M.  ATP binding and cross-bridge detachment steps during full Ca2+ activation: Comparison of myofibril and muscle fibre mechanics by sinusoidal analysis.  J Physiol (Lond).  2012. 590.14:3361–3373.
[PubMed]

Bai F, Groth H, Kawai M.  DCM-related tropomyosin mutants E40K/E54K over-inhibit the actomyosin interaction and lead to a decrease in the number of cycling cross-bridges.  PLoS ONE.  2012. 7:(e4741) 1-12.
[PubMed]

Candau R, Kawai M.  Correlation between cross-bridge kinetics obtained from Trp fluorescence of myofibril suspensions and mechanical studies of single muscle fibers in rabbit psoas.  J Muscle Res Cell Motil.  2011. 32:315-326.
[PubMed]

Bai F, Weis A, Takeda A, Chase B, Kawai M.  Enhanced active cross-bridges during diastole: molecular pathogenesis of tropomyosin’s HCM mutations.  Biophys J.  2011. 100:1014-1023.
[PubMed]

Muthus P, Wang L, Yuan C, Kazmierczak K, Huang W, Hernandez O, Kawai M, Irving T, Szczesna-Cordary D.  Structural and functional aspects of myosin ELC-mediated cardiac muscle contraction.  FASEB J .  2011. 11-191973:1-12.
[PubMed]

Oguchi Y, Ishizuka J, Hitchcock-DeGregori  S, Ishiwata S, Kawai M.  The role of tropomyosin domains in cooperative activation of the actin-myosin interaction.  J Mol Biol.  2011. 414:667-680.
[PubMed]

Kawai M, Candau R.  Muscle contraction and supplying ATP to muscle cells.  IOS Press.  2010. 

Lu X, Heeley D, Smillie L, Kawai M.  The role of tropomyosin isoforms and phosphorylation in force generation in thin-filament reconstituted bovine cardiac muscle fibres.  J Muscle Res Cell Motil.  2010. 31:93–109.
[PubMed]

Kawai M, Lu X, Hitchcock-DeGregori  S, Stanton K, Wandling M.  Tropomyosin period 3 is essential for enhancement of isometric tension in thin filament-reconstituted bovine myocardium.  J Biophysics.  2009. 2009:1-17.
[PubMed]

Kawai M, Halvorson H.  Force transients and minimum cross-bridge models in muscular contraction.  J Muscle Res Cell Motil.  2007. 28:371-395.
[PubMed]

Kawai M, Kido T, Vogel M, Fink R, Ishiwata S.  Temperature change does not affect force between regulated actin filaments and HMM in single molecule experiments.  J Physiol (Lond).  2006. 574.3:877–887.
[PubMed]

Lu X, Tobacman L, Kawai M.  Temperature dependence of isometric tension and cross-bridge kinetics of cardiac muscle fibers reconstituted with a tropomyosin internal deletion mutant.  Biophys J.  2006. 91(11):4230-4240.
[PubMed]

Kawai M, Ishiwata S.  Use of thin filament reconstituted muscle fibres to probe the mechanism of force generation.  J Muscle Res Cell Motil .  2006. 27:455-468.
[PubMed]

Galler S, Wang B, Kawai M.  Elementary steps of the cross-bridge cycle in fast-twitch fiber types from rabbit skeletal muscles.  Biophys J.  2005. 89:3248-3260.
[PubMed]

Lu X, Bryant M, Bryan K, Rubenstein P, Kawai M.  Role of the N-terminal negative charge of actin in cross-bridge kinetics and force generation in reconstituted bovine myocardium.  J Physiol (Lond).  2005. 564.1:65-82.
[PubMed]

Fujita H, Lu X, Suzuki M, Ishiwata S, Kawai M.  The effect of tropomyosin on force and elementary steps of the cross-bridge cycle in bovine myocardium.  J Physiol (Lond).  2004. 556.2:637-649.
[PubMed]

Lu X, Tobacman L, Kawai M.  Effects of tropomyosin internal deletion Δ23Tm on isometric tension and the cross-bridge kinetics in bovine myocardium.  J Physiol (Lond) .  2003. 553.2:457-471.
[PubMed]

Kawai M.  What do we learn by studying the temperature effect on isometric tension and tension transients in mammalian striated muscle fibres?.  J Muscle Res Cell Motil.  2003. 24:127-138.
[PubMed]

Fujita H, Sasaki D, Ishiwata S, Kawai M.  Elementary steps of the cross-bridge cycle in bovine myocardium with and without regulatory proteins..  Biophys J.  2002. 82(2):915-928.
[Link]

Fujita H, Kawai M.  Temperature effect on isometric tension is mediated by regulatory proteins tropomyosin and troponin in bovine myocardium.  J Physiol (Lond).  2002. 539.1:267-276.

Ding W, Fujita H, Kawai M.  The length of cooperative units on the thin filament in rabbit psoas muscle fibres.  Experimental Physiology.  2002. 87.6:691-697.
[Link]

Wang G, Kawai M.  Effect of temperature on elementary steps of the cross-bridge cycle in rabbit soleus slow-twitch muscle fibers..  J Phys.  2001. 531(1):219-234.
[Link]

Kawai M, Kawaguchi K, Saito M, Ishiwata S.  Temperature change does not affect force between single actin filaments and HMM from rabbit muscles..  Biophys J.  2000. 78:3112-3119.
[Link]

Wang G, Ding W, Kawai M.  Does thin filament compliance diminish the cross-bridge kinetics? A study in rabbit psoas fibers..  Biophys J.  1999. 76:978-984.
[Link]

Kawai M.  Comments on the paper by Dr. David Smith entitled, "A strain-dependent ratchet model for [phosphate]-and [ATP]-dependent muscle contraction..  J Muscle Res Cell Mot.  1998. 19:713-715.
[Link]

Kawai M.  Force generation and phosphate release steps in skinned rabbit soleus slow-twitch muscle fibres..  Biophys J.  1997. 73:878-894.

Wang G, Kawai M.  Effects of MgATP and MgADP on the cross-bridge kinetics of rabbit soleus slow-twitch muscle fibers..  Biophys J.  1996. 71:1450-1461.

Zhao Y, Kawai M.  Inotropic agent EMD-53998 weakens nucleotide and phosphate binding to cross-bridges in porcine myocardium..  Heart Circ Physiol.  1996. 271(4):H1394-1406.
[PubMed]

Murphy K, Zhao Y, Kawai M.  Molecular forces involved in force generation during skeletal muscle contraction..  J Exptl Biol.  1996. 199:2565-2571.
[Link]

Zhao Y, Swamy P, Humphries K, Kawai M.  The effect of partial extraction of troponin C on the elementary steps of the cross-bridge cycle in rabbit psoas fibers..  Biophys J.  1996. 71:2759-2773.
[Link]

Raucher D, Fajer E, Sar C, Hideg K, Zhao Y, Kawai M, Fajer P.  A novel electron paramagnetic resonance spin label and its application to study the cross-bridge cycle..  Biophys J.  1995. 
[Link]

Zhao Y, Kawai M.  BDM affects nucleotide binding and force generation steps of the cross-bridge cycle in rabbit psoas muscle fibers..  Am Physiol (Cell Physiol).  1994. 266(35):C437-C447.
[Link]

Zhao Y, Kawai M.  Kinetic and thermodynamic studies of the cross-bridge cycle in rabbit psoas muscle fibers..  Biophys J.  1994. 67:1655-1668.
[Link]

Schraeger J, Canby C, Rongish B, Kawai M, Tomanek R.  Normal left ventricular diastolic compliance following regression of hypertrophy. .  J Cardiovasc Pharm .  1994. 23(3):349-357.
[Link]

Kawai M, Zhao Y.  Cross-bridge scheme and force per cross-bridge state in skinned rabbit psoas muscle fibers..  Biophys J.  1993. 65(2):638-651.
[Link]

Kawai M, Saeki Y, Zhao Y.  Cross-bridge scheme and kinetic constants of elementary steps deduced from chemically skinned papillary and trabecular muscles of the ferret..  Circ Res.  1993. 73:35-50.
[Link]

Kawai M.  Kawai's response to Horiuti and Sakoda..  Biophys J.  1993. 65:2263-2264.
[Link]

Zhao Y, Kawai M.  The effect of the lattice spacing change on cross-bridge kinetics in chemically skinned rabbit psoas muscle fibers. Elementary steps affected by the spacing change..  Biophys J.  1993. 64(1):197-210.
[Link]

Kawai M, Wray J, Zhao Y.  The effect of the lattice spacing change on cross-bridge kinetics in chemically skinned rabbit psoas muscle fibers. I. Proportionality between the lattice spacing and the fiber width..  Biophys J.  1993. 64:187-196.
[Link]

Kawai M, Halvorson H.  Two step mechanism of phosphate release and the mechanism of force generation in chemically skinned rabbit psoas muscle..  Biophys J.  1991. 59(2):329-342.
[PubMed]

Date Last Modified: 03/10/2015 - 11:06:30