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    Last Name

    Mary Munson PhD

    TitleAssociate Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentBiochemistry and Molecular Pharmacology
    AddressUniversity of Massachusetts Medical School
    364 Plantation Street, LRB
    Worcester MA 01605
      Other Positions
      InstitutionUMMS - School of Medicine
      DepartmentCell and Developmental Biology

      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

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentProgram in Cell Dynamics


        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

        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)

        selected publications
        List All   |   Timeline
        1. Munson M. To protect or reject. Elife. 2014; 3:e03374.
          View in: PubMed
        2. Heider MR, Munson M. Exorcising the exocyst complex. Traffic. 2012 Jul; 13(7):898-907.
          View in: PubMed
        3. 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.
          View in: PubMed
        4. 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.
          View in: PubMed
        5. Munson M. Show me the MUN-y. Structure. 2011 Oct 12; 19(10):1348-9.
          View in: PubMed
        6. 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.
          View in: PubMed
        7. 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.
          View in: PubMed
        8. 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.
          View in: PubMed
        9. 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.
          View in: PubMed
        10. Munson M, Bolon DN. Watching proteins in motion. Genome Biol. 2009; 10(10):316.
          View in: PubMed
        11. 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.
          View in: PubMed
        12. 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.
          View in: PubMed
        13. Munson M, Bryant NJ. A role for the syntaxin N-terminus. Biochem J. 2009 Feb 15; 418(1):e1-3.
          View in: PubMed
        14. Croteau NJ, Furgason ML, Devos D, Munson M. Conservation of helical bundle structure between the exocyst subunits. PLoS One. 2009; 4(2):e4443.
          View in: PubMed
        15. Munson M. Tip20p reaches out to Dsl1p to tether membranes. Nat Struct Mol Biol. 2009 Feb; 16(2):100-2.
          View in: PubMed
        16. Songer JA, Munson M. Sec6p anchors the assembled exocyst complex at sites of secretion. Mol Biol Cell. 2009 Feb; 20(3):973-82.
          View in: PubMed
        17. 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.
          View in: PubMed
        18. Carr CM, Munson M. Tag team action at the synapse. EMBO Rep. 2007 Sep; 8(9):834-8.
          View in: PubMed
        19. 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.
          View in: PubMed
        20. 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.
          View in: PubMed
        21. Munson M, Novick P. The exocyst defrocked, a framework of rods revealed. Nat Struct Mol Biol. 2006 Jul; 13(7):577-81.
          View in: PubMed
        22. 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.
          View in: PubMed
        23. 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.
          View in: PubMed
        24. Munson M, Hughson FM. Conformational regulation of SNARE assembly and disassembly in vivo. J Biol Chem. 2002 Mar 15; 277(11):9375-81.
          View in: PubMed
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