Research Topics
| Henry HiggsSummaryAffiliation: Dartmouth Medical School Country: USA Publications
Research Grants
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Detail Information
Publications
Biochemical analysis of mammalian formin effects on actin dynamicsElizabeth S Harris
Dartmouth Medical School, Department of Biochemistry, Hanover, NH, USA
Methods Enzymol 406:190-214. 2006..The regulatory mechanisms for formins are not clear and certainly vary between isoforms. A subset of formins is regulated by Rho GTPases, and the assays described in this chapter have been used for characterization of this regulation...- Actin nucleation: nucleation-promoting factors are not all equalH N Higgs
Department of Biochemistry, 413 Vail Building, HB 7200, Dartmouth Medical School, Hanover, New Hampshire 03755 3844, USA
Curr Biol 11:R1009-12. 2001..A recent study has revealed marked differences in the ability of two nucleation-promoting factors - N-WASP and Scar/WAVE1 - to activate the Arp2/3 complex. Further insights have come from determination of the Arp2/3 crystal structure... - Formin proteins: a domain-based approachHenry N Higgs
Department of Biochemistry, Dartmouth Medical School, Hanover NH 03755, USA
Trends Biochem Sci 30:342-53. 2005..Other formins lack DAD, DID and GBD, and their regulatory mechanisms await elucidation... - Isoform-selective chemical inhibition of mDia-mediated actin assemblyTimothy J Gauvin
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
Biochemistry 48:9327-9. 2009..These results establish the druggability of mDia formins and introduce a first-generation inhibitor... - The mouse Formin mDia1 is a potent actin nucleation factor regulated by autoinhibitionFang Li
Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
Curr Biol 13:1335-40. 2003..RhoA partially relieves inhibition but does so when bound to either GDP or GTP analogs. Both N- and C-terminal mDia1 constructs appear to be multimeric... - Listeria motility: biophysics pushes things forwardAlexey J Merz
Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
Curr Biol 13:R302-4. 2003..The results also expose deficiencies in our understanding of this process, and suggest future directions for complete understanding of the molecular mechanisms involved... - Purification of recombinant acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1) from H293 cells and binding studies between the enzyme and substrates using difference intrinsic fluorescence spectroscopyCatherine C Y Chang
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, United States
Biochemistry 49:9957-63. 2010..These results show that stereospecificity, governed by the 3?-OH moiety in steroid ring A, plays an important role in the binding of cholesterol to ACAT1... - Actin nucleation: cortactin caught in the actHenry N Higgs
Dartmouth Medical School, Hanover, NH 03755 3844, USA
Curr Biol 12:R593-5. 2002..A variety of activators stimulate Arp2/3 complex to nucleate branched actin filament structures. New results provide important biochemical and structural information for activation by the proteins cortactin and N-WASP... - Phylogenetic analysis of the formin homology 2 domainHenry N Higgs
Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
Mol Biol Cell 16:1-13. 2005..This analysis allows for a formin nomenclature system based on sequence relationships, as well as suggesting strategies for the determination of biochemical and cellular activities of these proteins... - Mechanistic differences in actin bundling activity of two mammalian formins, FRL1 and mDia2Elizabeth S Harris
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
J Biol Chem 281:14383-92. 2006..Furthermore, our results suggest that the Ile mutation affects processivity. Taken together, our data suggest that the bundling activities of FRL1 and mDia2, while producing phenotypically similar bundles, differ in mechanistic detail... - Dissecting requirements for auto-inhibition of actin nucleation by the formin, mDia1Fang Li
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
J Biol Chem 280:6986-92. 2005..An additional finding is that FH2 domain-containing constructs of mDia1 and mDia2 lose >75% nucleation activity upon freeze-thaw... - The mouse formin, FRLalpha, slows actin filament barbed end elongation, competes with capping protein, accelerates polymerization from monomers, and severs filamentsElizabeth S Harris
Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
J Biol Chem 279:20076-87. 2004..FRLalpha-C's ability to sever filaments is the first such activity reported for any formin. Because we find that mDia1-C does not sever efficiently, severing may not be a property of all formins... - INF2 Is a WASP homology 2 motif-containing formin that severs actin filaments and accelerates both polymerization and depolymerizationEkta Seth Chhabra
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
J Biol Chem 281:26754-67. 2006..Third, INF2 contains an N-terminal DID, and the WH2 motif likely doubles as a DAD in an autoinhibitory interaction... - INF2 is an endoplasmic reticulum-associated formin proteinEkta Seth Chhabra
Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
J Cell Sci 122:1430-40. 2009..This study is the first to show the association of an actin-assembly factor with the ER... - The many faces of actin: matching assembly factors with cellular structuresEkta Seth Chhabra
Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
Nat Cell Biol 9:1110-21. 2007..Insights gained from studies of adherens junctions and the immunological synapse are also considered... - Actin dynamics: growth from dendritic branchesSusan Nicholson-Dykstra
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
Curr Biol 15:R346-57. 2005..In addition, actin dynamics at the leading edge might be influenced by a second actin filament network, independent of dendritic nucleation... - Lymphocyte microvilli are dynamic, actin-dependent structures that do not require Wiskott-Aldrich syndrome protein (WASp) for their morphologySonja Majstoravich
Department of Biochemistry HB7200, Dartmouth Medical School, Hanover, NH 03755 3844, USA
Blood 104:1396-403. 2004..These results suggest that WASp is either not involved in or is redundant in the rapid dynamics of lymphocyte microvilli... - Tropomyosin regulates elongation by formin at the fast-growing end of the actin filamentBarbara Wawro
Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, New Jersey 08854, USA
Biochemistry 46:8146-55. 2007..This role, in addition to its cooperative control of myosin function, establishes tropomyosin as a universal regulator of the multifaceted actin cytoskeleton... - Dia-interacting protein modulates formin-mediated actin assembly at the cell cortexKathryn M Eisenmann
Laboratory of Cell Structure and Signal Integration, Van Andel Research Institute, Grand Rapids, MI 49503, USA
Curr Biol 17:579-91. 2007..Dia-interacting protein (DIP) binds via its amino-terminal SH3 domain to the proline-rich formin homology 1 (FH1) domain of mDia1 and mDia2 and to the N-WASp proline-rich region... - There goes the neighbourhood: Eps8 joins the barbed-end crowdHenry N Higgs
Nat Cell Biol 6:1147-9. 2004 - Ena/VASP proteins enhance actin polymerization in the presence of barbed end capping proteinsMelanie Barzik
Department of Biology, University of Virginia, Charlottesville, Virginia 22903, USA
J Biol Chem 280:28653-62. 2005..We propose that Ena/VASP proteins associate at or near actin filament barbed ends, promote actin assembly, and restrict the access of barbed end capping proteins... - Control of the assembly of ATP- and ADP-actin by formins and profilinDavid R Kovar
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA
Cell 124:423-35. 2006..These results suggest that diverse formins are mechanistically similar, but the rates of particular assembly steps vary...
Research Grants
- Comparative molecular physiology of mammalian forminsHenry Higgs; Fiscal Year: 2007..Biochemical results from Aims 1 and 2 will provide the basis for the cellular studies in Aim 3. ..
- Comparative molecular physiology of mammalian forminsHenry Higgs; Fiscal Year: 2009..Our findings provide new and exciting opportunities for therapies against pathologies involving malfunction of these mechanisms. ..
- Comparative molecular physiology of mammalian forminsHenry Higgs; Fiscal Year: 2009..My laboratory studies how actin polymerization is controlled in specific processes. By understanding these processes, I hope to develop therapeutic interventions for diseases such as cancer and immunological diseases. ..
- Comparative molecular physiology of mammalian forminsHenry N Higgs; Fiscal Year: 2010..Our findings provide new and exciting opportunities for therapies against pathologies involving malfunction of these mechanisms. ..