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Mary Munson PhD

TitleProfessor
InstitutionUniversity of Massachusetts Medical School
DepartmentBiochemistry and Molecular Pharmacology
AddressUniversity of Massachusetts Medical School
364 Plantation Street, LRB
Worcester MA 01605
Phone508-856-8318
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    Other Positions
    InstitutionUMMS - School of Medicine
    DepartmentBiochemistry and Molecular Pharmacology

    InstitutionUMMS - School of Medicine
    DepartmentNeuroNexus Institute

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentBiochemistry and Molecular Pharmacology

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentCell Biology

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentInterdisciplinary Graduate Program

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentTranslational Science


    Collapse Biography 
    Collapse education and training
    Washington University in St Louis, Saint Louis, MO, United StatesABChemistry & Biology
    Yale University, New Haven, CT, United StatesPHDMolecular Biophysics & Biochem

    Collapse Overview 
    Collapse overview

    Academic Background

    Mary Munson was a double major in Chemistry and Biology at Washington University(St. Louis), receiving her bachelor's degree in 1989. In 1996, she received her Ph.D.from Yale University in Molecular Biophysics and Biochemistry. She was a postdoctoral fellow in the Department of Molecular Biology at Princeton University, where she was awarded both American Heart Association and NIH postdoctoral fellowships. She joined the faculty of Biochemistry and Molecular Pharmacology in 2001.

    Regulation of vesicle targeting and fusion

    Vesicle targeting and fusion are tightly regulated processes used by eukaryotic cells to transport cargo between membrane-bound subcellular compartments and to the plasma membrane for secretion. The proper function and specificity of these processes are crucial for maintenance of cellular integrity, normal growth, and for intercellular signaling events, such as neurotransmission.

    We are interested in understanding the mechanistic basis for regulation of the spatial and temporal specificity of vesicle fusion, at the correct site on the target membrane. Many questions remain to be answered. For example, what marks the site of fusion on the target membrane? What checks to make sure that the correct vesicle docks at the right place? How are the membrane fusion proteins regulated to ensure that the wrong vesicle does not fuse? Our aim is to answer questions such as these through a multifaceted approach that combines biochemical, structural and biophysical techniques with yeast genetics, microscopy and cell biological methods. We are investigating proteins that regulate exocytosis in the model organism Saccharomyces cerevisiae. Because these proteins are conserved from yeast to man, these studies will advance our understanding of how secretion is regulated in all eukaryotic cells.

    Our Research

    Our investigations mainly focus on the Exocyst complex (Fig. 1), a protein complex essential for vesicle trafficking (exocytosis) in all eukaryotes. The proteins that form the Exocyst complex localize to secretory vesicles and to sites of active secretion at bud tips and mother-bud necks. These proteins are essential for cell viability, show physical and genetic interactions with the the membrane fusion proteins (SNAREs) and with each other, and their temperature-sensitive mutants have secretory blocks and accumulate secretory vesicles.

    Our research has several aims: 1) biophysical and structural studies of the Exocyst proteins and their interactions with each other; 2) creation and testing of mutants in vivo, in order to elucidate the functions of the Exocyst proteins; 3) characterization of interactions between the Exocyst and other proteins required for exocytosis, such as the SNARE proteins, and regulators such as Sec1p and the small Rab GTPase Sec4p; and 4) genetic and proteomic identification of novel regulators of exocytosis and SNARE complex assembly. Additionally, we are characterizing the regulation of endocytosis by the Sec1-homolog Vps45p, through its interactions with the endosomal SNARE proteins.

    Figure 1.Current model for the architecture of the exocyst complex

    Current model for the architecture of the exocyst complex



    Collapse Rotation Projects

    Potential Rotation Projects

    Research in the Munson lab is focused on biochemical/biophysical and cell biological characterization of proteins in the exocyst complex. Potential rotation projects include the following:

    • Cloning of various exocyst protein domains and point mutations. These will be expressed in E. coli for biochemical/structural studies, and their functions tested in yeast.
    • Protein expression and purification. Develop purification strategies for several exocyst proteins and their domains, using chromatography methods such as ion exchange and gel filtration (Fig. 2).
    • Characterization of the purified exocyst proteins. Protein structure, stability, oligomerization state and protein:protein interactions will be monitored by such techniques as circular dichroism, analytical ultracentrifugation and gel filtration (Fig. 3).
    • Crystallography. We have determined the structure of the C-terminal domain of Sec6p (Fig. 4). Crystallization trials ofotherexocyst proteins and their domains are in progress.
    • Design and test functional exocyst mutants in yeast. Mutants will be characterized using a variety of biochemical, cell biological, and microscopic techniques.
    • Identify novel regulators of yeast exocytosis using a genetic screen. Mutants created in these screens are currently being tested and identified (Fig. 5). Their role in exocytosis will be explored

    Gel Filtration Curve Circular dichroism spectrum

    Structure of the C-terminal domain of Sec6pMutant yeast cannot lose the covering plasmid (red)




    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Lepore DM, Martínez-Núñez L, Munson M. Exposing the Elusive Exocyst Structure. Trends Biochem Sci. 2018 Jul 25. PMID: 30055895.
      View in: PubMed
    2. Yoon TY, Munson M. SNARE complex assembly and disassembly. Curr Biol. 2018 Apr 23; 28(8):R397-R401. PMID: 29689222.
      View in: PubMed
    3. Parchure A, Munson M, Budnik V. Getting mRNA-Containing Ribonucleoprotein Granules Out of a Nuclear Back Door. Neuron. 2017 Nov 01; 96(3):604-615. PMID: 29096075.
      View in: PubMed
    4. Boehm CM, Obado S, Gadelha C, Kaupisch A, Manna PT, Gould GW, Munson M, Chait BT, Rout MP, Field MC. The Trypanosome Exocyst: A Conserved Structure Revealing a New Role in Endocytosis. PLoS Pathog. 2017 Jan; 13(1):e1006063. PMID: 28114397.
      View in: PubMed
    5. Dubuke ML, Munson M. The Secret Life of Tethers: The Role of Tethering Factors in SNARE Complex Regulation. Front Cell Dev Biol. 2016; 4:42. PMID: 27243006.
      View in: PubMed
    6. Heider MR, Gu M, Duffy CM, Mirza AM, Marcotte LL, Walls AC, Farrall N, Hakhverdyan Z, Field MC, Rout MP, Frost A, Munson M. Subunit connectivity, assembly determinants and architecture of the yeast exocyst complex. Nat Struct Mol Biol. 2016 Jan; 23(1):59-66. PMID: 26656853.
      View in: PubMed
    7. Bombardier JP, Munson M. Three steps forward, two steps back: mechanistic insights into the assembly and disassembly of the SNARE complex. Curr Opin Chem Biol. 2015 Dec; 29:66-71. PMID: 26498108.
      View in: PubMed
    8. Dubuke ML, Maniatis S, Shaffer SA, Munson M. The Exocyst Subunit Sec6 Interacts with Assembled Exocytic SNARE Complexes. J Biol Chem. 2015 Nov 20; 290(47):28245-56. PMID: 26446795.
      View in: PubMed
    9. Munson M. Synaptic-vesicle fusion: a need for speed. Nat Struct Mol Biol. 2015 Jul; 22(7):509-11. PMID: 26150331.
      View in: PubMed
    10. Munson M. To protect or reject. Elife. 2014; 3:e03374. PMID: 24940001.
      View in: PubMed
    11. Heider MR, Munson M. Exorcising the exocyst complex. Traffic. 2012 Jul; 13(7):898-907. PMID: 22420621.
      View in: PubMed
    12. Jin Y, Sultana A, Gandhi P, Franklin E, Hamamoto S, Khan AR, Munson M, Schekman R, Weisman LS. Myosin V transports secretory vesicles via a Rab GTPase cascade and interaction with the exocyst complex. Dev Cell. 2011 Dec 13; 21(6):1156-70. PMID: 22172676.
      View in: PubMed
    13. Morgera F, Sallah MR, Dubuke ML, Gandhi P, Brewer DN, Carr CM, Munson M. Regulation of exocytosis by the exocyst subunit Sec6 and the SM protein Sec1. Mol Biol Cell. 2012 Jan; 23(2):337-46. PMID: 22114349.
      View in: PubMed
    14. Munson M. Show me the MUN-y. Structure. 2011 Oct 12; 19(10):1348-9. PMID: 22000505.
      View in: PubMed
    15. Yang Y, Xia F, Hermance N, Mabb A, Simonson S, Morrissey S, Gandhi P, Munson M, Miyamoto S, Kelliher MA. A cytosolic ATM/NEMO/RIP1 complex recruits TAK1 to mediate the NF-kappaB and p38 mitogen-activated protein kinase (MAPK)/MAPK-activated protein 2 responses to DNA damage. Mol Cell Biol. 2011 Jul; 31(14):2774-86. PMID: 21606198.
      View in: PubMed
    16. Heuck A, Fetka I, Brewer DN, Hüls D, Munson M, Jansen RP, Niessing D. The structure of the Myo4p globular tail and its function in ASH1 mRNA localization. J Cell Biol. 2010 May 3; 189(3):497-510. PMID: 20439999.
      View in: PubMed
    17. MacDonald C, Munson M, Bryant NJ. Autoinhibition of SNARE complex assembly by a conformational switch represents a conserved feature of syntaxins. Biochem Soc Trans. 2010 Feb; 38(Pt 1):209-12. PMID: 20074061.
      View in: PubMed
    18. Shandilya SM, Nalam MN, Nalivaika EA, Gross PJ, Valesano JC, Shindo K, Li M, Munson M, Royer WE, Harjes E, Kono T, Matsuo H, Harris RS, Somasundaran M, Schiffer CA. Crystal structure of the APOBEC3G catalytic domain reveals potential oligomerization interfaces. Structure. 2010 Jan 13; 18(1):28-38. PMID: 20152150.
      View in: PubMed
    19. Munson M, Bolon DN. Watching proteins in motion. Genome Biol. 2009; 10(10):316. PMID: 19863776.
      View in: PubMed
    20. Furgason ML, MacDonald C, Shanks SG, Ryder SP, Bryant NJ, Munson M. The N-terminal peptide of the syntaxin Tlg2p modulates binding of its closed conformation to Vps45p. Proc Natl Acad Sci U S A. 2009 Aug 25; 106(34):14303-8. PMID: 19667197.
      View in: PubMed
    21. Struthers MS, Shanks SG, MacDonald C, Carpp LN, Drozdowska AM, Kioumourtzoglou D, Furgason ML, Munson M, Bryant NJ. Functional homology of mammalian syntaxin 16 and yeast Tlg2p reveals a conserved regulatory mechanism. J Cell Sci. 2009 Jul 1; 122(Pt 13):2292-9. PMID: 19509055.
      View in: PubMed
    22. Munson M, Bryant NJ. A role for the syntaxin N-terminus. Biochem J. 2009 Feb 15; 418(1):e1-3. PMID: 19159342.
      View in: PubMed
    23. Croteau NJ, Furgason ML, Devos D, Munson M. Conservation of helical bundle structure between the exocyst subunits. PLoS One. 2009; 4(2):e4443. PMID: 19214222.
      View in: PubMed
    24. Munson M. Tip20p reaches out to Dsl1p to tether membranes. Nat Struct Mol Biol. 2009 Feb; 16(2):100-2. PMID: 19190660.
      View in: PubMed
    25. Songer JA, Munson M. Sec6p anchors the assembled exocyst complex at sites of secretion. Mol Biol Cell. 2009 Feb; 20(3):973-82. PMID: 19073882.
      View in: PubMed
    26. Redfern RE, Redfern D, Furgason ML, Munson M, Ross AH, Gericke A. PTEN phosphatase selectively binds phosphoinositides and undergoes structural changes. Biochemistry. 2008 Feb 19; 47(7):2162-71. PMID: 18220422.
      View in: PubMed
    27. Carr CM, Munson M. Tag team action at the synapse. EMBO Rep. 2007 Sep; 8(9):834-8. PMID: 17767192.
      View in: PubMed
    28. Togneri J, Cheng YS, Munson M, Hughson FM, Carr CM. Specific SNARE complex binding mode of the Sec1/Munc-18 protein, Sec1p. Proc Natl Acad Sci U S A. 2006 Nov 21; 103(47):17730-5. PMID: 17090679.
      View in: PubMed
    29. Pan X, Eathiraj S, Munson M, Lambright DG. TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism. Nature. 2006 Jul 20; 442(7100):303-6. PMID: 16855591.
      View in: PubMed
    30. Munson M, Novick P. The exocyst defrocked, a framework of rods revealed. Nat Struct Mol Biol. 2006 Jul; 13(7):577-81. PMID: 16826234.
      View in: PubMed
    31. Sivaram MV, Furgason ML, Brewer DN, Munson M. The structure of the exocyst subunit Sec6p defines a conserved architecture with diverse roles. Nat Struct Mol Biol. 2006 Jun; 13(6):555-6. PMID: 16699513.
      View in: PubMed
    32. Sivaram MV, Saporita JA, Furgason ML, Boettcher AJ, Munson M. Dimerization of the exocyst protein Sec6p and its interaction with the t-SNARE Sec9p. Biochemistry. 2005 Apr 26; 44(16):6302-11. PMID: 15835919.
      View in: PubMed
    33. Munson M, Hughson FM. Conformational regulation of SNARE assembly and disassembly in vivo. J Biol Chem. 2002 Mar 15; 277(11):9375-81. PMID: 11777922.
      View in: PubMed
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