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cell biology : faculty

Postdoctoral
Position
Available

Mary Munson, Ph.D.

Academic Role: Assistant Professor

Faculty Appointment(s) In:
   Biochemistry and Molecular Pharmacology

Other Affiliation(s):
   Cell Biology
   Cell Dynamics Group
   Interdisciplinary Graduate Program

Regulation of vesicle targeting and fusion

Photo: Mary Munson

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. Many key mechanistic issues are poorly understood. What controls the specificity of vesicle targeting to the correct membrane? What determines the site of fusion on the membrane? How are vesicles docked? How are docking and fusion regulated? Our aim is to answer questions such as these through a multifaceted approach that combines biochemical and biophysical techniques with yeast genetics 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 investigations focus on the Exocyst complex (Fig. 1) which is required for vesicle trafficking 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, they show genetic interactions with the 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, which are core components of the vesicle fusion machinery, and regulators such as Sec1p and the small GTPase Sec4p; and 4) identification of novel regulators of exocytosis and SNARE complex assembly .

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

Current model for the architecture of the exocyst complex


 

                      

 

  

 

 


Representative Publications

M. Munson. “Tip20p reaches out to Dsl1p to tether membranes .” Nature Struct Mol Biol, 16:100-102, 2009.

N. Croteau, M.L.M. Furgason, D. Devos and M. Munson.   “Conservation of helical bundle structure between the exocyst subunits. ” PLoS ONE, 4:e4443, 2009.

M. Munson and N.J. Bryant. “A role for the syntaxin N-terminus .” Biochem J, 418:e1-3, 2009.

J. Songer and M. Munson. “Sec6p anchors the exocyst complex at sites of secretion .”  Mol Biol Cell, 20:973-982, 2009.

C.M. Carr and M. Munson (2007). “Tag team action at the synapse .” EMBO Reports, 8:834-8        

J. Togneri, Y.S. Cheng, M. Munson, F.M. Hughson and C.M. Carr (2006). “Specific SNARE complex binding mode of the Sec1/Munc-18 protein, Sec1p. ” Proc Natl Acad Sci USA, 103:17730-5.

M.V.S. Sivaram, M.L.M. Furgason, D.N. Brewer, and M. Munson (2006). “The structure of the exocyst subunit Sec6p defines a conserved architecture with diverse roles .” Nat Struct Mol Biol, 13:555-556.

M. Munsonand P. Novick (2006). “The Exocyst defrocked, a framework of rods revealed .” Nat Struct Mol Biol, 13: 577-581.

X. Pan, S. Eathiraj, M. Munson, and D.G. Lambright (2006). “TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism. ” Nature, 442:303-306.

A. Gericke, M. Munson, and A.H. Ross (2006). “Regulation of the PTEN phosphatase .” Gene, 374:1-9.

M.V.S. Sivaram, J.A. Saporita, M.L.M. Furgason, A.J. Boettcher, and M. Munson (2005),Dimerization of the exocyst protein Sec6p and its interaction with the t-SNARE Sec9p .  Biochemistry. 44: 6302–6311.

M. Munson and F.M. Hughson (2002), Conformational regulation of SNARE assembly and disassembly in vivo. J Biol Chem, 277: 9375-9381 .

M. Munson*, X. Chen*, S. Schultz, A.E. Cocina, and F.M. Hughson (2000) "Interactions within the yeast t-SNARE Sso1p that control SNARE complex assembly ." Nature Structural Biology. 7: 894-902 .

C.M. Carr, E. Grote, M. Munson, F.M. Hughson and P.J. Novick (1999) "Sec1p Binds to SNARE Complexes and Concentrates at Sites of Secretion. " J Cell Biology. 146: 333-344.

K.L. Nicholson, M. Munson, R.B. Miller, T.J. Filip, R. Fairman, and F.M. Hughson (1998) "Regulation of SNARE complex assembly by an N-terminal domain of the t-SNARE Sso1p. " Nature Structural Biology. 5: 793-802.

M.W. Klemba*, M. Munson*, and L. Regan. (1998) "De novo design of protein structure and function." In: Proteins: Analysis and Design. (Ed. by R.H. Angeletti), Academic Press, N.Y., N.Y.

M. Munson, K. Anderson, and L. Regan (1997) "Speeding up protein folding: mutations that increase the rate at which Rop folds and unfolds by over four orders of magnitude ." Folding & Design 2: 77-87.

M. Munson, S. Balasubramanian, K.G. Fleming, A.D. Nagi, R. O' Brien, J.M. Sturtevant and L. Regan (1996) "What makes a protein a protein? Hydrophobic core designs that specify stability and structural properties. " Protein Science 5: 1584-1593.

C.K. Smith, M. Munson, and L. Regan (1995) "Studying a-helix and b-sheet formation in small proteins." In: Techniques in Protein Chemistry, Vol VI, p. 323-332.

M. Munson, R. O'Brien, J.M. Sturtevant, and L. Regan (1994) "Redesigning the hydrophobic core of a four-helix-bundle protein. " Protein Science 3: 2015-2022.

M. Munson, P.F. Predki, and L. Regan (1994) "ColE1-compatible vectors for high-level expression of cloned DNAs from the T7 promoter. " Gene 144: 59-62.

(* indicates authors contributed equally)


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 of other exocyst 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 Sec6p Mutant yeast cannot lose the covering plasmid (red)

                                          

 


Laboratory Staff

Munson Lab

Munson lab, summer 2005

(left to right) Dan Brewer, Amanda Tichy, Jen Songer, Mary Munson, Melonnie Furgason,Sivaram Mylavarapu, and Jamie Towle

Dan Brewer, Graduate Student
Melonnie Furgason, Graduate Student
Jen Songer, Graduate Student
Amanda Tichy, Undergradute at Worcester Polytechnic Institute '08 atichy@wpi.edu


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.


Office: LRB 905, Lab 970-Y, 940 A
Phone: 508-856-8318
E-mail: Mary.Munson@umassmed.edu
Keywords: Intracellular Trafficking, Biophysics, Cell Biology, Biochemistry, Structural Biology

More on Mary Munson's Research
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Postdoctoral Position Available

A postdoctoral position is available to study in this laboratory. Contact Dr. Munson for additional details.

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