Sacher, Michael - Concordia University

研究领域

A eukaryotic cell is composed of many different compartments (eg. nucleus, mitochondria, Golgi apparatus, vacuole, endoplasmic reticulum). Each of these organelles is surrounded by a membrane, thus separating the inside of the organelle from the cytoplasm. Furthermore, each compartment contains its own unique protein and lipid composition. Material can be transferred between specific organelles by small vesicles that bud from one compartment and fuse with another compartment. Faulty sorting of this material leads to numerous human diorders and is a fundamental process in cell biology. The main question in our research is: how is the specificity in vesicle targeting ensured? We focus on a protein complex called TRAPP and are actively studying the functions of the components of this complex, several of which have been implicated in human disorders. Therefore, our work involves model systems as well as cells derived from patients with TRAPP subunit mutations.

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Liang, W.C., Zhu, W., Mitsuhashi, S., Noguchi, S., Sacher, M., Ogawa, M., Shih,H.H., Jong, Y.J. and Nishino, I. (2015) Congenital muscular dystrophy with fatty liver and infantile-onset cataract caused by TRAPPC11 mutations: broadening of the phenotype. Skeletal Muscle 5, Aug. 2015 Milev,M., Hasaj,B., Saint-Dic,D.,Snounou,S., Zhao,Q. and Sacher,M. (2015) TRAMM/TrappC12 plays a role inchromosome congression, kinetochore stability and CENP-E recruitment J. Cell Biol. 209, 221-234 Brunet,S. and Sacher,M. (2014) Insickness and in health: The role of TRAPP and associated proteins in disease. Traffic 15, 803-818 Bögershausen,N.,Shahrzad,N., Chong,J.X., vonKleist-Retzow,J.-C., Stanga,D., Li,Y., Bernier,F.P., Loucks,C.M.,Wirth,R., Puffenberger,E.G.,Hegele,R., Schreml,J., Lapointe,G.,Keupp,K., Brett,C.L.,Anderson,R., Hahn,A., Innes,A.M.,Suchowersky,O., Mets,M.B., Nürnberg,G.,McLeod,D.R., Thiele,H.,Waggoner,D., Altmüller,J.,Boycott,K.M., Schoser,B., Nürnberg,P.,Ober,C., Heller,R., Parboosingh,J.S.,Wollnik,B., Sacher,M. and Lamont,R.E.(2013) Recessive TRAPPC11 mutations cause a disease spectrum of limb girdlemuscular dystrophy and myopathy with movement disorder and intellectualdisability. Am. J. Hum. Genet. 93, 181-190 Brunet,S., Shahrzad,N., St.-Dic,D.,Dutczak,H. and Sacher,M. (2013) A trs20mutation in Saccharomyces cerevisiaethat mimics an SEDT-causing mutation destabilizes TRAPP III and blocks both selectiveand non-selective autophagy: a model for TRAPP III organization. Traffic 19, 1091-1104 Brunet,S., Noueihed,B., Shahrzad,N., Saint-Dic,D., Hasaj,B., Guan,T.-L., Moores,A., Barlowe,C. and Sacher,M. (2012) The SMS domain of Trs23p is responsible for the in vitro appearance of the TRAPP I complex in Saccharomyces cerevisiae Cell. Log., 2, 28-42 Scrivens,P.J., Shahrzad,N., Moores,A., Morin,A., Brunet,S. and Sacher,M. (2009) TRAPPC2L is a novel, highly conserved TRAPP-interacting protein Traffic, 10, 724-736 Sacher,M., Kim,Y.-G., Lavie,A., Oh,B.-H. and Segev,N. (2008) The TRAPP complex: insights into its architecture and function Traffic, 9, 2032-2042 Kim,Y.-G., Raunser,S., Munger,C., Wagner,J., Song,Y.-L., Cygler,M., Walz,T., Oh,B.-H. and Sacher,M. (2006) The architecture of the multisubunit TRAPP I complex suggests a model for vesicle tethering Cell 127, 817-830 Kim, M.-S., Yi, M.-J., Lee, K.-H., Wagner, J., Munger, C., Kim, Y.-G., Whiteway, M., Cygler, M., Oh, B.-H. and Sacher, M. 2005. Biochemical and crystallographic studies reveal a specific interaction between TRAPP subunits Trs33p and Bet3p. Traffic, 6, 1183-1195   Kim, Y.-G., Sohn ,E.J., Seo, J., Lee, K.-J., Lee, H.-S., Hwang, I., Whiteway, M., Sacher, M. and Oh, B.-H. 2005. Crystal structure of bet3 reveals a novel mechanism for Golgi localization of tethering factor TRAPP. Nature Struct. Mol. Biol. 12, 38-45   Sacher, M., Barrowman, J., Wang, W., Horecka, J., Zhang, Y., Pypaert ,M. and Ferro-Novick, S. 2001. TRAPP I implicated in the specificity of tethering in ER-to-Golgi transport. Mol. Cell, 7, 433-442   Barrowman, J., Sacher, M. and Ferro-Novick, S. 2000. TRAPP stably associates with the Golgi and is required for vesicle docking. EMBO J. 19, 862-869   Sacher, M., Jiang, Y., Barrowman, J., Scarpa, A., Burston, J., Zhang, L., Schieltz, D., Yates III, J.R., Abeliovich, H. and Ferro-Novick, S. 1998. TRAPP, a highly conserved novel complex on the cis-Golgi that mediates vesicle docking and fusion. EMBO J. 17, 2494-2503