Protein trafficking in disease

The highly co-ordinated movement of the thousands of distinct membrane proteins between the cell surface and intracellular compartments is a critical factor in health and disease. This movement controls the organisation of cells in tissues and communication between cells and their environment. The success of this process depends on the regulated sorting and trafficking of proteins within the highly dynamic endosomal compartments of the cell in processes that are emerging as important drivers of neurodegenerative disease, cancer and metabolic pathologies. An understanding of how endosomal traffic is regulated, and how lysosomal traffic and degradation are modulated, is critical for providing insights into disease and devising new therapeutic approaches.

  • Chen KE, Guo Q, Hill TA, Cui Y, Kendall AK, Yang Z, Hall RJ, Healy MD, Sacharz J, Norwood SJ, Fonseka S, Xie B, Reid RC, Leneva N, Parton RG, Ghai R, Stroud DA, Fairlie DP, Suga H, Jackson LP, Teasdale RD, Passioura T, Collins BM. De novo macrocyclic peptides for inhibiting, stabilizing, and probing the function of the retromer endosomal trafficking complex. Science Advances. (2021) 7 eabg4007.
  • Cui Y, Yang Z, Flores-Rodriguez N, Follett J, Ariotti N, Wall AA, Parton RG, Teasdale RD. Formation of retromer transport carriers is disrupted by the Parkinson disease-linked Vps35 D620N variant. Traffic. (2021) 22 123-136.
  • Yang Z, Li Z, Teasdale RD Retromer dependent changes in cellular homeostasis and Parkinson's disease. Essays in Biochemestry. (2021) 65 987-998
  • Cui Y, Carosi JM, Yang Z, Ariotti N, Kerr MC, Parton RG, Sargeant TJ, Teasdale RD Retromer has a selective function in cargo sorting via endosome transport carriers. Journal of Cell Biology. (2019) 218 615-631.
  • Kovtun O, Leneva N, Bykov YS, Ariotti N, Teasdale RD, Schaffer M, Engel BD, Owen DJ, Briggs JAG, Collins BM. Structure of the membrane-assembled retromer coat determined by cryo-electron tomography. Nature. (2018) 561 561-564.
  • Kerr MC, Gomez GA, Ferguson C, Tanzer MC, Murphy JM, Yap AS, Parton RG, Huston WM, Teasdale, R.D. Laser-mediated rupture of chlamydial inclusions triggers pathogen egress and host cell necrosis. Nature Communications (2017) 8 14729.
  • Yang Z, Hong LK, Follett J, Wabitsch M, Hamilton NA, Collins BM, Bugarcic A, Teasdale, R.D. Functional characterization of retromer in GLUT4 storage vesicle formation and adipocyte differentiation. FASEB Journal (2016) 30 1037 – 1050.
  • Follett J, Bugarcic A, Yang Z, Ariotti N, Norwood SJ, Collins BM, Parton RG, Teasdale, R.D. Parkinson Disease-linked Vps35 R524W Mutation Impairs the Endosomal Association of Retromer and Induces α-Synuclein Aggregation. Journal of Biological Chemistry (2016) 291 18283 – 18298.
  • Follett J, Norwood SJ, Hamilton NA, Mohan M, Kovtun O, Tay S, Zhe Y, Wood SA, Mellick GD, Silburn PA, Collins BM, Bugarcic A, Teasdale, R.D. The Vps35 D620N Mutation Linked to Parkinson's Disease Disrupts the Cargo Sorting Function of Retromer. Traffic (2014) 15 230 – 244.
  • Kerr M., Teasdale, R.D. Live imaging of endosome dynamics. Seminars In Cell and Developmental Biology (2014) 31 11 – 19.
  • Teasdale, R.D. and Collins, B.C. Insights into the PX (phox-homology) domain and SNX (sorting nexin) protein families: structures, functions and roles in disease. Biochemistry Journal (2012) 441 39 – 59.
  • Bugarcic A., Zhe Y., Kerr M.C., Griffin J., Collins B.M., and Teasdale, R.D. Vps26A and Vps26B Subunits Define Distinct Retromer Complexes. Traffic (2011) 12 1759 – 1773.
  • Kerr M.C., Wang, J.T.H., Castro, N., Hamilton, N.A., Town, L., Brown, D.L., Meunier, F.A., Brown, N.F., Stow, J.L. and Teasdale, R.D. Inhibition of the PtdIns(5) kinase PIKfyve disrupts intracellular replication of Salmonella. The EMBO Journal (2010) 8 295 1331 – 1347.
  • Wang J.T., Kerr M.C., Karunaratne S., Jeanes A., Yap A.S., and Teasdale, R.D. The SNX-PX-BAR family in macropinocytosis: the regulation of macropinosome formation by SNX-PX-BAR proteins. PLoS One (2010) 5 e13763 -.
  • Kerr M.C., and Teasdale, R.D. Defining macropinocytosis. Traffic (2009) 10 364 – 371.
  • Fink, J.L., Karunaratne, S., Mittal, A., Gardiner, D., Hamilton, N., Mahony,D., Kai, C., Suzuki, H., Hayashizaki, Y. and Teasdale, R.D. Towards defining the nuclear proteome. Genome Biology (2008) 9 R15 -.
  • Kerr, M.C., Bennetts, J.C., Simpson, F., Thomas, E.C., Flegg, C., Gleeson, P.A, Wicking, C., and Teasdale, R.D. A Novel Mammalian Retromer Component, Vps26B. Traffic (2005) 6 991 – 1001.
  • Teasdale, R.D., Loci, D., Karlsson, L. and Gleeson, P.A. A large family of endosomal localised proteins related to sorting nexin 1. Biochemical Journal (2001) 358 7 – 16.

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