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Top blue bar image Department of Biochemistry & Cell Biology
 

James McNew

Associate Professor in Biochemistry and Cell Biology

My lab is interested in the molecular mechanisms of membrane fusion. Membrane fusion is a fundamental process involved in diverse cellular events such as fertilization and neuroscretion. Biological membrane fusion relies on proteins to drive membrane merger. mcnew_workA family of integral membrane proteins collectively known as SNAREs mediates the fusion of intracellular transport vesicles. While SNAREs pair in specific ways to provide the mechanical energy to drive fusion, the delicate interplay of regulatory elements that orchestrate this event in space and time remain elusive. We use biochemistry, cell biology and molecular genetic techniques to study the assembly and regulation of SNARE proteins in two model systems: vesicular transport in the budding yeast S. cerevisiae and neurosecretion in the fruity D. melanogaster. We have initially focused our attention on the regulatory role of Sec1p in yeast exocytosis. We have recently shown that Sec1p binds primarily to the yeast t-SNARE complex and directly stimulates membrane fusion. We are currently examining the precise method of Sec1p stimulation as well as analyzing the function of the Sec1p family member ROP in neuronal exocytosis. Additional studies in the lab involve membrane fusion events in other aspects of yeast cell biology including sporulation and cell-cell fusion during mating.

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McNew JA, Sondermann H, Lee T, Stern M, Brandizzi F. GTP-dependent membrane fusion.  Annu Rev Cell Dev Biol, 29 2013: 529-550

Shen D, Yuan H, Hutagalung A, Verma A, Kümmel D, Wu X, Reinisch K, McNew JA, Novick P. The synaptobrevin homologue Snc2p recruits the exocyst to secretory vesicles by binding to Sec6p.  J Cell Biol, 202(3) 2013: 509-26

Faust, J.E., Peng, C., and McNew, J.A. An inventory of peroxisomal proteins and pathways in Drosophila melanogaster.  Traffic 2012

Stefano, G., Renna, L., Moss, T.J., McNew, J.A., and Brandizzi, F. In Arabidopsis the spatial and dynamic organization of the Endoplasmic Reticulum and Golgi apparatus is influenced by the integrity of he C-terminal domain of RHD3, a non-essential GTPase.  Plant J., 69 2012: 957-966

Pendin, D., McNew, J.A. and Daga, A. Balancing ER dynamics: shaping, bending, severing, and mending membranes.  Curr Opin Cell Biol 2011

Pendin, D., Tosetto, J., Moss, T.J., Andreazza, C., Moro, S., McNew, J.A., and Daga, A. GTP-dependant packing of a 3-helix bundle is required for atlastin mediated fusion.  Natl Acad Sci USA, 108 2011: 16283-88

Moss, T.J., Andreazza, C., Verma, A., Daga, A. and McNew, J.A. Membrane fusion by the GTPase atlastin requires a conserved C-terminal cytoplasmic tail and dimerization through the middle domain.  Proc Natl Acad Sci USA, 108 2011: 11133-38

Nair, U., A. Jotwani, J. Geng, N. Gammoh, D. Richerson, W.L. Yen, J. Griffith, S. Nag, K. Wang, T. Moss, M. Baba, J.A. McNew, X. Jiang, F. Reggiori, T.J. Melia, and D.J. Klionsky SNARE proteins are required for macroautophagy.  Cell, 146 2011: 290-302

Orso, G., Pendin, D., Liu, S., Tosetto, J., Moss, T.J., Faust, J.E., Micaroni, M., Polishchuk, R.S., Martinuzzi, A., McNew, J.A., and Daga, A. The dynamin-like GTPase atlastin is required for homotypic fusion of endoplasmic reticulum membranes.  Nature, 460 2009: 978-983

Yang, H.J., Nakanishi, H., Liu, S., McNew, J.A., and Neiman, A.M. Binding interactions control SNARE specificity in vivo.  J. Cell. Biol., 183 (6) 2008: 1089-1100

Rodkey, T.L., Liu, S., Barry, M., and McNew, J.A. Munc18a scaffolds SNARE assembly to promote membrane fusion.  Molecular Biology of the Cell, 19 (12) 2008: 5422-5434

Brandie, F.M., Aran, V., Verma, A., McNew, J.A., Bryant, N.J., and Gould, G.W. Negative regulation of syntaxin4/SNAP-23/VAMP2-mediated membrane fusion by Munc18c in vitro.  PLoS One, 3 (12) 2008: e4074

McNew, J.A. (2008). Regulation of SNARE-Mediated Membrane Fusion during Exocytosis. Chem Rev.

McNew, J.A. Regulation of SNARE-mediated membrane fusion during exocytosis.  Chem. Rev., 108 (5) 2008: 1669-1686

Curtis, L.B., Doneske, B., Liu, X., Thaller, C., McNew, J.A., and Janz, R. Syntaxin 3B is a t-SNARE specific for ribbon synapses of the retina.  J. Comp. Neurol., 510 (5) 2008: 550-559

Liu, S., Wilson, K.A., Rice-Stitt, T., Neiman, A.N., and McNew, J.A. In vitro fusion by the sporulation specific t-SNARE light chain Spo20p is stimulated by phosphatidic acid.  Traffic, 8 2007: 1630-1643

Van Komen, J.S., Bai, X., Scott, B.L., and McNew, J.A. An intramolecular t-SNARE complex functions in vivo without the syntaxin N-terminal regulatory domain.  J. Cell Biol., 172 2006: 295-307

Schaub, J.R., Lu,X., Doneske, B., Shin, Y-K., and McNew, J.A. Hemifusion arrest by complexin is relieved by Ca2+-Synaptotagmin I.  Nature Structural & Molecular Biology, 13 2006: 748-750

Xu, Y., Zhang, F., Su, Z., McNew, J.A., and Shin, Y.K. Hemifusion in SNARE-mediated membrane fusion.  Nat. Struct. Mol. Biol., 12 2005: 417-422

Lu, C., Zhang, F., McNew, J.A., and Shin, Y.K. Membrane fusion induced by neuronal SNAREs transits through hemifusion.  J. Biol. Chem., 280 2005: 30538-30541

Van Komen, J.S., Bai, X., Rodkey, T.L., Schaub, J., and McNew, J.A. The polybasic juxtamembrane region of Sso1p is required for SNARE function in vivo.  Eukaryotic Cell, 4 2005: 2017-2028

Yan, Q., Sun, W., McNew, J.A., Vida, T.A., and Bean, A.J. Ca2+ and N-ethylmaleimide-sensitive factor differentially regulate disassembly of SNARE complexes on early endosomes.  J. Biol. Chem., 279 2004: 18270-18276

McCartney, A.W., Dyer, J.M., Dhanoa, P.K., Kim, P.K., Andrews, D.W., McNew, J.A., and Mullen, R.T. Membrane-bound fatty acid desaturases are inserted co-translationally into the ER and contain different ER retrieval motifs at their carboxy termini.  Plant J., 37 2004: 156-173

Scott, B.L., Van Komen, J.S., Irshad, H., Liu, S., Wilson, K.A., and McNew, J.A. Sec1p directly stimulates SNARE-mediated membrane fusion in vitro.  J. Cell Biol., 167 2004: 75-85

Scott, B.L., Van Komen, J.S., Liu, S., Weber, T., Melia, T. J., and McNew, J. A. A liposome fusion assay to monitor intracellular membrane fusion machines.  Methods in Enzymology, 372 2003: 274-300

Parlati, F., Varlamov, O., Paz, K., McNew, J.A., Hurtado, D., Sollner, T.H., and Rothman, J.E. Distinct SNARE complexes mediating membrane fusion in Golgi transport based on combinatorial specificity.  Proc. Natl. Acad. Sci. U.S.A., 99 2002: 5424-5429

Melia, T.J., Weber, T., McNew, J.A., Sollner, T.H., and Rothman, J.E. Regulation of membrane fusion by the membrane-proximal coil of the t-SNARE during zippering of SNAREpins.  J. Cell Biol., 158 2002: 929-940

Paumet, F., Brugger, B., Parlati, F., McNew, J.A., Sollner, T., and Rothman, J.E. A t-SNARE of the endocytic pathway must be activated for fusion.  J. Cell Biol., 155 2001: 961-968

McNew, J.A., Weber., T., Parlati, F., Johnston, R.J., Melia, T.J., Sollner, T.H., and Rothman, J.E. Close is not enough: SNARE-dependent membrane fusion requires an active mechanism that transduces force to membrane anchors.  Journal of Cell Biology, 150 2000: 105-117

McNew, J.A., Parlati, F., Fukuda, R., Johnston, R.J., Paz, K., Paumet, F., Sollner, T.H., and Rothman, J.E. Compartmental specificity of cellular membrane fusion encoded in SNARE proteins.  Nature, 407 2000: 153-159

Fukuda, R., McNew, J.A., Weber, T., Parlati, F., Engel, T., Nickel, W., Rothman, J.E., and Sollner, T.H. Functional architecture of an intracellular t-SNARE.  Nature, 407 2000: 198-202

Brugger, B., Nickel, W., Weber, T., Parlati, F., McNew, J.A., Rothman, J.E., and Sollner, T.H. Putative fusogenic activity of NSF is restricted to a lipid mixture whose coalescence is also triggered by other factors.  EMBO J., 19 2000: 1272-1278

Weber, T., Parlati, F., McNew, J.A., Johnston, R.J., Westermann, B., Sollner, T.H., and Rothman, J.E. SNAREpins are functionally resistant to disruption by NSF and alphaSNAP.  J. Cell Biol., 149 2000: 1063-1072

Parlati, F., McNew, J.A., Fukuda, R., Miller, R., Sollner, T.H., and Rothman, J.E. Topological restriction of SNARE-dependent membrane fusion.  Nature, 407 2000: 194-198

Nickel, W., Weber, T., McNew, J.A., Parlati, F., Sollner, T.H., and Rothman, J.E. Content mixing and membrane integrity during membrane fusion driven by pairing of isolated v-SNAREs and t-SNAREs.  Proc. Natl. Acad. Sci. USA, 96 1999: 12571-12576

Parlati, F., Weber, T., McNew, J.A., Westermann, B., Sollner, T.H., and Rothman, J.E. Rapid and efficient fusion of phospholipid vesicles with the alpha-Helical core domain of a SNARE complex in the absence of an N-terminal regulatory domain.  Proc. Natl. Acad. Sci. USA, 96 1999: 12565-12570

McNew, J.A., Weber, T., Engelman, D.M., Sollner, T.H., and Rothman, J.E. The length of the flexible SNAREpin juxtamembrane region is a critical determinant of SNARE-dependent membrane fusion.  Mol. Cell, 4 1999: 415-421

McNew, J.A., Coe, J.G.S., Sogaard, M., Zemelman, B.V., Wimmer, C., Hong, W., and Sollner, T.H. Gos1p, a Saccharomyces cerevisiae SNARE protein involved in Golgi transport.  FEBS Lett., 435 1998: 89-95

Weber, T., Zemelman, B.V., McNew, J.A., Westermann, B., Gmachl, M., Parlati, F., Sollner, T.H, and Rothman, J.E. SNAREpins: Minimal machinery for membrane fusion.  Cell, 92 1998: 759-772

McNew, J.A., Hartmann, E., and Sollner, T.H. Vesicular flow patterns in yeast delineated by SNAREs.  Chemtracts-Biochemistry and Molecular Biology, 11 1998: 446-458

Lupashin, V.V., Pokravskaya, I.D., McNew, J.A., and Waters, M.G. Characterization of a novel yeast SNARE protein implicated in Golgi retrograde traffic.  Molec. Biol. Cell, 8 1997: 2659-2676

McNew, J.A., Sogaard, M., Lampen, N.M., Machido, S., Ye, R.R., Lacomis, L., Tempst, P., Rothman, J.E., and Sollner, T.H. Ykt6p, a prenylated SNARE essential for endoplasmic reticulum-Golgi transport.  J. Biol. Chem., 272 1997: 17776-17783

Faust, J.E., Manisundaram, A., Stern, M., and McNew, J.A. Peroxisome Biogenesis in Drosophila melanogaster.   March 7-11, 2012

McNew Lab

  • Postdoctoral Training Cell Biology (1995-2000) Memorial Sloan-Kettering Cancer Center
  • B.S. Biochemistry (1989) Texas A&M University
  • Ph.D. Pharmacology (1994) University of Texas Southwestern Medical Center
  • Institute of Biosciences and Bioengineering
  • Molecular mechanism of biological membrane fusion. Peroxisome biogenesis. membrane protein expression and reconstitution, intracellular vesicular transport, ER homotypic fusion
Email: mcnew@rice.edu
Phone: 713-348-3133
Office: Bioscience Research Collaborative, Room 713