MICHAEL D FORGAC

Summary

Affiliation: Tufts University
Country: USA

Publications

  1. ncbi request reprint Subunit D (Vma8p) of the yeast vacuolar H+-ATPase plays a role in coupling of proton transport and ATP hydrolysis
    T Xu
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Biol Chem 275:22075-81. 2000
  2. ncbi request reprint Vacuolar ATPases: rotary proton pumps in physiology and pathophysiology
    Michael Forgac
    Department of Physiology, Tufts University School of Medicine, 136 Harrison Ave, Boston, Massachusetts 02111, USA
    Nat Rev Mol Cell Biol 8:917-29. 2007
  3. ncbi request reprint V-ATPase functions in normal and disease processes
    Ayana Hinton
    Department of Physiology, Tufts University School of Medicine, 136 Harrison Ave, Boston, MA 02111, USA
    Pflugers Arch 457:589-98. 2009
  4. ncbi request reprint TM2 but not TM4 of subunit c'' interacts with TM7 of subunit a of the yeast V-ATPase as defined by disulfide-mediated cross-linking
    Yanru Wang
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Biol Chem 279:44628-38. 2004
  5. pmc Subunit H of the vacuolar (H+) ATPase inhibits ATP hydrolysis by the free V1 domain by interaction with the rotary subunit F
    Kevin C Jefferies
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Biol Chem 283:4512-9. 2008
  6. ncbi request reprint Subunit a of the yeast V-ATPase participates in binding of bafilomycin
    Yanru Wang
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Biol Chem 280:40481-8. 2005
  7. ncbi request reprint Cysteine-mediated cross-linking indicates that subunit C of the V-ATPase is in close proximity to subunits E and G of the V1 domain and subunit a of the V0 domain
    Takao Inoue
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Biol Chem 280:27896-903. 2005
  8. ncbi request reprint Involvement of the nonhomologous region of subunit A of the yeast V-ATPase in coupling and in vivo dissociation
    Elim Shao
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Biol Chem 279:48663-70. 2004
  9. ncbi request reprint Localization of subunits D, E, and G in the yeast V-ATPase complex using cysteine-mediated cross-linking to subunit B
    Yoichiro Arata
    Department of Physiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, Massachusetts 02111, USA
    Biochemistry 41:11301-7. 2002
  10. ncbi request reprint Proton translocation driven by ATP hydrolysis in V-ATPases
    Shoko Kawasaki-Nishi
    Department of Physiology, Tufts University School of Medicine, 136 Harrison Ave, Boston, MA 02111, USA
    FEBS Lett 545:76-85. 2003

Research Grants

  1. Conference--Molecular & Cellular Bioenergetics
    Michael Forgac; Fiscal Year: 2003
  2. STRUCTURE, MECHANISM AND REGULATION OF THE V-ATPASES
    Michael Forgac; Fiscal Year: 2007

Collaborators

  • S Wilkens
  • Souad R Sennoune
  • Yanru Wang
  • Jie Qi
  • Takao Inoue
  • Tsuyoshi Nishi
  • Ayana Hinton
  • Sarah Bond
  • Shoko Kawasaki-Nishi
  • Kevin C Jefferies
  • Daniel J Cipriano
  • Masashi Toei
  • Elim Shao
  • Yoichiro Arata
  • Ruichao Shen
  • James D Baleja
  • Regina Saum
  • T Xu
  • RAUL MARTINEZ-ZAGUILAN
  • Min Fang
  • Daniel Jay
  • Moshe Reuveni
  • G Gary Sahagian
  • John A Porco
  • Kevin Jefferies

Detail Information

Publications29

  1. ncbi request reprint Subunit D (Vma8p) of the yeast vacuolar H+-ATPase plays a role in coupling of proton transport and ATP hydrolysis
    T Xu
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Biol Chem 275:22075-81. 2000
    ..These results suggest that subunit D plays an important role in coupling of proton transport and ATP hydrolysis and that only low rates of turnover of the enzyme are required to support in vivo dissociation...
  2. ncbi request reprint Vacuolar ATPases: rotary proton pumps in physiology and pathophysiology
    Michael Forgac
    Department of Physiology, Tufts University School of Medicine, 136 Harrison Ave, Boston, Massachusetts 02111, USA
    Nat Rev Mol Cell Biol 8:917-29. 2007
    ..The V-ATPases have been implicated in a number of diseases and, coupled with their complex isoform composition, represent attractive and potentially highly specific drug targets...
  3. ncbi request reprint V-ATPase functions in normal and disease processes
    Ayana Hinton
    Department of Physiology, Tufts University School of Medicine, 136 Harrison Ave, Boston, MA 02111, USA
    Pflugers Arch 457:589-98. 2009
    ..Plasma membrane V-ATPases have also been implicated in tumor cell invasion. V-ATPases are thus emerging as potential targets in the treatment of diseases such as osteoporosis and cancer...
  4. ncbi request reprint TM2 but not TM4 of subunit c'' interacts with TM7 of subunit a of the yeast V-ATPase as defined by disulfide-mediated cross-linking
    Yanru Wang
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Biol Chem 279:44628-38. 2004
    ..These results are discussed in terms of a model involving rotation of interacting helices in subunit a and the proteolipid subunits relative to each other...
  5. pmc Subunit H of the vacuolar (H+) ATPase inhibits ATP hydrolysis by the free V1 domain by interaction with the rotary subunit F
    Kevin C Jefferies
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Biol Chem 283:4512-9. 2008
    ..These results indicate that subunits H and F are proximal in free V1, supporting the hypothesis that subunit H inhibits free V1 by bridging the rotary and stator domains...
  6. ncbi request reprint Subunit a of the yeast V-ATPase participates in binding of bafilomycin
    Yanru Wang
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Biol Chem 280:40481-8. 2005
    ..84 +/- 0.04 nm) that was slightly higher than wild-type (0.60 +/- 0.07 nm). These results suggest that subunit a of V-ATPase participates along with subunit c in binding bafilomycin...
  7. ncbi request reprint Cysteine-mediated cross-linking indicates that subunit C of the V-ATPase is in close proximity to subunits E and G of the V1 domain and subunit a of the V0 domain
    Takao Inoue
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Biol Chem 280:27896-903. 2005
    ..The localization of subunit C to the interface of the V1 and V0 domains is consistent with a role for this subunit in controlling assembly of the V-ATPase complex...
  8. ncbi request reprint Involvement of the nonhomologous region of subunit A of the yeast V-ATPase in coupling and in vivo dissociation
    Elim Shao
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Biol Chem 279:48663-70. 2004
    ..The results suggest that the dependence of in vivo dissociation of the V-ATPase on catalytic activity may be due to neutralization of the yeast vacuole, which in turn blocks glucose-dependent dissociation...
  9. ncbi request reprint Localization of subunits D, E, and G in the yeast V-ATPase complex using cysteine-mediated cross-linking to subunit B
    Yoichiro Arata
    Department of Physiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, Massachusetts 02111, USA
    Biochemistry 41:11301-7. 2002
    ..Subunit D is thus the most likely homologue to the gamma subunit of F(1), which undergoes rotation during ATP hydrolysis and serves an essential function in rotary catalysis...
  10. ncbi request reprint Proton translocation driven by ATP hydrolysis in V-ATPases
    Shoko Kawasaki-Nishi
    Department of Physiology, Tufts University School of Medicine, 136 Harrison Ave, Boston, MA 02111, USA
    FEBS Lett 545:76-85. 2003
    ..This review is focused on the current structural knowledge of the V-ATPases as it relates to the mechanism of ATP-driven proton translocation...
  11. ncbi request reprint The vacuolar (H+)-ATPase: subunit arrangement and in vivo regulation
    Jie Qi
    Department of Physiology, Tufts University School of Medicine, 136 Harrison Ave, Boston, MA 02111, USA
    J Bioenerg Biomembr 39:423-6. 2007
    ..The dependence of reversible dissociation on subunit isoforms and cellular environment has been investigated...
  12. ncbi request reprint Cysteine-directed cross-linking to subunit B suggests that subunit E forms part of the peripheral stalk of the vacuolar H+-ATPase
    Yoichiro Arata
    Departments of Physiology and Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Biol Chem 277:3357-63. 2002
    ..This location for subunit E suggests that this subunit forms part of the peripheral stalk of the V-ATPase that links the V(1) and V(0) domains...
  13. pmc Function, structure and regulation of the vacuolar (H+)-ATPases
    Kevin C Jefferies
    Department of Physiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
    Arch Biochem Biophys 476:33-42. 2008
    ..V-ATPases are emerging as potential drug targets in treating a number of human diseases including osteoporosis and cancer...
  14. pmc Structure and regulation of the vacuolar ATPases
    Daniel J Cipriano
    Department of Physiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
    Biochim Biophys Acta 1777:599-604. 2008
    ..This review focuses on recent advances in our lab in understanding the structure and regulation of the V-ATPases...
  15. pmc Function and subunit interactions of the N-terminal domain of subunit a (Vph1p) of the yeast V-ATPase
    Jie Qi
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Biol Chem 283:19274-82. 2008
    ..These results suggest that a localized region of the N-terminal domain (residues 347-369) is important in anchoring the peripheral stator in V1V0...
  16. pmc Analysis of the membrane topology of transmembrane segments in the C-terminal hydrophobic domain of the yeast vacuolar ATPase subunit a (Vph1p) by chemical modification
    Yanru Wang
    Department of Physiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
    J Biol Chem 283:20696-702. 2008
    ..The results support an eight transmembrane helix (TM) model of subunit a in which the C terminus is located on the cytoplasmic side of the membrane and provide information on the location of hydrophilic loops separating TM6, 7, and 8...
  17. pmc The Ras/cAMP/protein kinase A pathway regulates glucose-dependent assembly of the vacuolar (H+)-ATPase in yeast
    Sarah Bond
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Biol Chem 283:36513-21. 2008
    ..These results reveal a role for PKA in controlling glucose-dependent V-ATPase assembly in yeast...
  18. pmc Function of a subunit isoforms of the V-ATPase in pH homeostasis and in vitro invasion of MDA-MB231 human breast cancer cells
    Ayana Hinton
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Biol Chem 284:16400-8. 2009
    ..However, other V-ATPases affecting the pH of the cytosol and intracellular compartments, particularly those containing a3, are also involved in invasion...
  19. ncbi request reprint The vacuolar (H+)-ATPases--nature's most versatile proton pumps
    Tsuyoshi Nishi
    Department of Physiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, Massachusetts 02111, USA
    Nat Rev Mol Cell Biol 3:94-103. 2002
    ..Recent advances in our understanding of the structure and regulation of the V-ATPases, together with the mapping of human genetic defects to genes that encode V-ATPase subunits, have led to tremendous excitement in this field...
  20. ncbi request reprint Expression and function of the mouse V-ATPase d subunit isoforms
    Tsuyoshi Nishi
    Department of Physiology, Tufts University School of Medicine, Boston, MA 02111, USA
    J Biol Chem 278:46396-402. 2003
    ..These results suggest that subunit d may play a role in coupling of proton transport and ATP hydrolysis...
  21. ncbi request reprint Subunit structure, function, and arrangement in the yeast and coated vesicle V-ATPases
    Takao Inoue
    Department of Physiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, Massachusetts 02111, USA
    J Bioenerg Biomembr 35:291-9. 2003
    ..We have also investigated the mechanism of regulation of the V-ATPase by reversible dissociation and the role of different subunits in this process...
  22. ncbi request reprint Interacting helical surfaces of the transmembrane segments of subunits a and c' of the yeast V-ATPase defined by disulfide-mediated cross-linking
    Shoko Kawasaki-Nishi
    Department of Physiology, Tufts University School of Medicine, Boston, MA 02111, USA
    J Biol Chem 278:41908-13. 2003
    ..The results are consistent with a possible rotational flexibility of one or both of these transmembrane segments as well as some flexibility of movement perpendicular to the membrane...
  23. ncbi request reprint Synthesis of photoactivatable acyclic analogues of the lobatamides
    Ruichao Shen
    Department of Chemistry and Center for Chemical Methodology and Library Development, Boston University, 590 Commonwealth Avenue, Boston, Massachusetts 02215, USA
    J Org Chem 70:3686-92. 2005
    ..Analogues 3-5 were also evaluated for inhibition of bovine V-ATPase in order to select a suitable candidate for future photoaffinity labeling studies...
  24. ncbi request reprint Mutational analysis of the non-homologous region of subunit A of the yeast V-ATPase
    Elim Shao
    Department of Physiology, Tufts University School of Medicine, Boston Massachusetts 02111, USA
    J Biol Chem 278:12985-91. 2003
    ..These results suggest that changes in the non-homologous region can also alter in vivo dissociation of the V-ATPase independent of effects on activity...
  25. ncbi request reprint The first putative transmembrane segment of subunit c" (Vma16p) of the yeast V-ATPase is not necessary for function
    Tsuyoshi Nishi
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Biol Chem 278:5821-7. 2003
    ..These results suggest that subunit c" contains four rather than five transmembrane segments with both the N and C terminus on the cytoplasmic side of the membrane...
  26. ncbi request reprint Structure and regulation of the V-ATPases
    Takao Inoue
    Department of Physiology, Tufts University School of Medicine, 136 Harrison Ave, Boston, Massachusetts 02111, USA
    J Bioenerg Biomembr 37:393-8. 2005
    ..With respect to regulation of V-ATPase activity, we have investigated the role that intracellular environment, luminal pH and a unique domain of the catalytic A subunit play in controlling reversible dissociation in vivo...
  27. pmc Cellular environment is important in controlling V-ATPase dissociation and its dependence on activity
    Jie Qi
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Biol Chem 282:24743-51. 2007
    ..Moreover, catalytic activity is not absolutely required for V-ATPase dissociation...
  28. pmc Arrangement of subunits in the proteolipid ring of the V-ATPase
    Yanru Wang
    Department of Physiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
    J Biol Chem 282:34058-65. 2007
    ..These results suggest that functionally assembled V-ATPase complexes contain the proteolipid subunits arranged in a unique order in the ring...
  29. pmc Regulation and isoform function of the V-ATPases
    Masashi Toei
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    Biochemistry 49:4715-23. 2010
    ..This review will begin with a brief introduction to the function, structure, and mechanism of the V-ATPases followed by a discussion of the role of V-ATPase subunit isoforms and the mechanisms involved in regulation of V-ATPase activity...

Research Grants3

  1. Conference--Molecular & Cellular Bioenergetics
    Michael Forgac; Fiscal Year: 2003
    ....
  2. STRUCTURE, MECHANISM AND REGULATION OF THE V-ATPASES
    Michael Forgac; Fiscal Year: 2007
    ..These studies should provide further insight into the structure and regulation of this important family of (fP)-ATPases. ..