Peter Rubenstein Laboratory

  • rubenstein
  • Research Interests

    My research focuses on the factors that determine actin function in muscle and nonmuscle cells. We use site-directed mutagenesis coupled with a yeast expression system to make specific changes in yeast actin and to then assess the effects of these mutations in vivo and in vitro. Specific on-going projects involve a determination of the factors that allow formation of stable actin filaments, the role of the bound nucleotide in actin function, and the postulated role of tropomyosin as an actin-filament stabilizing protein.


    Figure Legend.. Tryptic peptide digest of wild-type and two mutant yeast actins with altered amino terminal regions. Mutations were made using site-directed mutagenesis. Arrows denote the peptides in which the mutations are located. A: wild-type actin; B: D2 and E4 altered to N and Q respectively; C: D2 - E4 deleted

    Recent Publications

    Rubenstein P, Wen K.  Mutant vascular actin is a TAAD misbehaving..  Proceedings of the National Academy of Sciences of the United States of America.  2015 August 4. 112(31):9500-1. [PubMed]

    Rubenstein P, Wen K.  Insights into the effects of disease-causing mutations in human actins.  Cytoskeleton (Hoboken).  2014 February 25. [PubMed]

    Yamashiro S, Gokhin D, Sui Z, Bergeron S, Rubenstein P, Fowler V.  Differential actin-regulatory activities of Tropomodulin1 and Tropomodulin3 with diverse tropomyosin and actin isoforms.  J Biol Chem.  2014. 289(17):11616-29. [PubMed]

    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. [PubMed]

    Wen K, McKane M, Rubenstein P.  Importance of a Lys113-Glu195 Intermonomer Ionic Bond in F-actin Stabilization and Regulation by Yeast Formins Bni1p and Bnr1p.  The Journal of Biological Chemistry.  2013 June. 288(26):19140-53. [PubMed]

    Johnston J, Wen K, Keppler-Noreuil K, McKane M, Maiers J, Greiner A, Sapp J.  Functional Analysis of a De Novo ACTB Mutation in a Patient with Atypical Baraitser-Winter Syndrome.  Human Mutation.  2013 May. doi: 10.1002/humu.22350. [PubMed]

    Lee C, Lou J, Wen K, McKane M, Eskin S, Ono S, Chien S, Rubenstein P, Zhu C, McIntire L.  Actin depolymerization under force is governed by lysine 113:glutamic acid 195-mediated catch-slip bonds.  Proceedings of the National Academy of Sciences of the United States of America.  2013 March. 110(13):5022-7. [PubMed]

    Rubenstein P, Mayer E.  Familial visceral myopathies: From symptom-based syndromes to actin-related diseases.  Gastroenterology.  2012 December. 143(6). [PubMed]

    Glenn N, McKane M, Kohli V, Wen K, Rubenstein P, Bartman T, Sumanas S.  The W-loop of alpha-cardiac actin is critical for heart function and endocardial cushion morphogenesis in zebrafish.  Molecular and Cellular Biology.  2012 September. 32(17):3527-40. [PubMed]

    Malloy L, Wen K, Pierick A, Wedemeyer E, Bergeron S, Vanderpool N, McKane M, Rubenstein P, Bartlett H.  Thoracic aortic aneurysm (TAAD)-causing mutation in actin affects formin regulation of polymerization.  The Journal of Biological Chemistry.  2012 August. 287(34):28398-408. [PubMed]

    Kruth K, Rubenstein P.  Two deafness-causing (DFNA20/26) actin mutations affect Arp2/3-dependent actin regulation.  The Journal of Biological Chemistry.  2012 August. 287(32):27217-26. [PubMed]

    Wen K, McKane M, Stokasimov E, Rubenstein P.  Mutant profilin suppresses mutant actin-dependent mitochondrial phenotype in Saccharomyces cerevisiae.  The Journal of Biological Chemistry.  2011 December. 286(48):41745-57. [PubMed]

    Stark B, Wen K, Allingham J, Rubenstein P, Lord M.  Functional adaptation between yeast actin and its cognate myosin motors.  The Journal of Biological Chemistry.  2011 September. 286(35):30384-92. [PubMed]

    Bergeron SE, Wedemeyer EW, Lee R, Wen KK, McKane M, Pierick AR, Berger AP, Rubenstein PA, Bartlett HL. (2011) Allele-specific effects of thoracic aortic aneurysm and dissection (TAAD) {alpha}-smooth muscle actin mutations on actin function. J Biol Chem. Feb 2, [Epub ahead of print] Download pdf reprint

    Wen KK, McKane M, Stokasimov E, Fields J, Rubenstein PA. (2010) A potential yeast actin allosteric conduit dependent on hydrophobic core residues V76 and W79. J Biol Chem. May 4. [Epub ahead of print]. Download pdf reprint

    Bergeron SE, Zhu M, Thiem SM, Friderici KH, Rubenstein PA. (2010) Ion-dependent polymerization differences between mammalian beta- and gamma-nonmuscle actin isoforms. J Biol Chem. May 21;285(21):16087-95. Download pdf reprint

    Wen KK, Rubenstein PA, DeMali KA. (2009) Vinculin nucleates actin polymerization and modifies actin filament structure. J Biol Chem. Oct 30; 284(44):30463-73. Download pdf reprint

    Stokasimov E, Rubenstein PA. (2009) Actin isoform-specific conformational differences observed with hydrogen/deuterium exchange and mass spectrometry. J Biol Chem. Sep 11;284(37):25421-30. Download pdf reprint

    Morín M, Bryan KE, Mayo-Merino F, Goodyear R, Mencía A, Modamio-Høybjør S, del Castillo I, Cabalka JM, Richardson G, Moreno F, Rubenstein PA, Moreno-Pelayo MA. (2009) In vivo and in vitro effects of two novel gamma-actin (ACTG1) mutations that cause DFNA20/26 hearing impairment. Hum Mol Genet. Aug 15;18(16):3075-89. Download pdf reprint

    Bryan KE, Rubenstein PA. (2009) Allele-specific effects of human deafness gamma-actin mutations (DFNA20/26) on the actin/cofilin interaction. J Biol Chem. Jul 3;284(27):18260-9. Download pdf reprint

    Wen KK, Rubenstein PA. (2009) Differential regulation of actin polymerization and structure by yeast formin isoforms. J Biol Chem. Jun 19;284(25):16776-83.Download pdf reprint

    Scoville D, Stamm JD, Altenbach C, Shvetsov A, Kokabi K, Rubenstein PA, Hubbell WL, Reisler E. (2009) Effects of binding factors on structural elements in F-actin. Biochemistry. Jan 20;48(2):370-8.

    Stokasimov E, McKane M, Rubenstein PA. (2008) Role of intermonomer ionic bridges in the stabilization of the actin filament. J Biol Chem. Dec 12;283(50):34844-54. Download pdf reprint

    Shvetsov, A., Galkin, V.C., Orlova, A., Phillips, M., Bergeron, S.E., Rubenstein, P.A., Egelman, E.H., and Reisler, E. (2008) Actin hydrophobic loop 262-274 and filament nucleation and elongation. J. Mol. Biol. 375:793-801. Download pdf reprint

    Wen, K.K., McKane, M., Houtman, J.C. and Rubenstein, P.A. (2008) Control of the ability of profilin to bind and facilitate nucleotide exchange from G-actin. J. Biol. Chem. 283-9444-9453. Download pdf reprint

    Scoville, D., Stamm, J.D., Toledo-Warshaviak, D., Altenbach, C., Phillips, M., Shvetsov, A., Rubenstein, P.A., Hubbell, W.L., and Reisler, E. (2006) Hydrophobic loops dynamics and actin filament stability. Biochemistry 45:13576-13584. Download pdf reprint

    McKane, M., Wen, K.K., Meyer, A., and Rubenstein, P.A. (2006) Effect of the substitute of muscle-actin-specific subdomain 1 and 2 residues in yeast actin on actin function. J. Biol. Chem. 281:29916-29928. Download pdf reprint

    Bryan, K.E., Wen, K.-K., Zhu, M., Rendtorff, N.D., Feldkamp, M., Tranebjaerg, L., Friderici, K.H., and Rubenstein, P.A. (2006) Effects of human deafness g-actin mutations (DFNA20/26) on actin function. J. Biol. Chem. 281:20129-20139. Download pdf reprint

    Chen, W., Wen, K.-K., Sens, A.E., and Rubenstein, P.A. (2006) Differential interactions of cardiac, skeletal muscle and yeast tropomyosins with fluorescent (Pyrene235) yeast actin. Biophys. J. 90:1308-1318. Download pdf reprint

    Shvetsov, A., Stamm, J.D., Phillips, M., Warshaviak, D., Altenbach, C., Rubenstein, P.A., Hideg, K., Hubbell, W.L., and Reisler, E. (2006) Conformational dynamics of loop 262 - 274 in G- and F-actin. Biochemistry 45:6541-6549. Download pdf reprint

    McKane, M., Wen, K.-K., Boldogh, I.R., Ramcharan, S., Pon, L.A., and Rubenstein, P.A. (2005) A mammalian actin substitution in yeast actin (H372R) causes a suppressible mitochondria/vacuole phenotype. J. Biol. Chem. 280:36494-36501. Download pdf reprint

    Rubenstein, P.A. and Wen, K.K. (2005) Lights, camera, actin. IUBMB Life 57:683-687. Download pdf reprint

    Wen, K.-K. and Rubenstein, P.A. (2005) Acceleration of yeast actin polymerization by yeast Arp2/3 complex does not require an Arp2/3-activating protein. J. Biol. Chem. 280:24168-24174. Download pdf reprint

    Lu, X., Bryant, M.K., Bryan, K., Rubenstein, P.A., and Kawai, M. (2005) Role of the N-terminal negative charges of actin in force generation and cross-bridge kinetics in reconstituted bovine cardiac muscle fibres. J. Physiol. 564:65-82. Download pdf reprint

    Bryan, K.E. and Rubenstein, P.A. (2005) An intermediate form of ADP-F actin. J. Biol. Chem 280:1696-1703. Download pdf reprint

    Secondary Appointment

    Internal Medicine