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513 Stellar-Chance Labs/6100 |
The secretory and endocytic pathways of eukaryotic cells are compartmentalized into distinct membrane-bound organelles and vesicular structures, each with its own characteristic function and macromolecular composition. We are interested in how proteins and protein complexes are assembled, modified, and sorted to the appropriate compartments, and how these processes contribute to the biogenesis of specific organelles and suborganellar structures. A major goal is to understand the nature of the cellular machinery involved in protein sorting and organelle biogenesis through genetic, cellular and biochemical approaches. Our efforts in this area are currently focused on the generation of lysosome-related organelles using melanosomes of pigmented cells as the model system. These organelles provide useful models for understanding how genetic diseases alter sorting processes required for organelle formation. Moreover, fibrillar structures within melanosomes resemble amyloid that forms under pathological conditions such as Alzheimer's and Parkinson's disease, and their formation serves as a model for understanding the basis for such diseases. A second focus in the lab is on understanding molecular mechanisms regulating protein recycling from endosomes to the trans Golgi network of all cells and how conserved proteins called golgins contribute to these mechanisms. Selected Publications: Setty, SRG, D Tenza, ST Truschel, EM Chou, EV Sviderskaya, AC Theos, ML Lamoreux, SM Di Pietro, M Starcevic, DC Bennett, EC Dell'Angelica, G Raposo and MS Marks (2007) BLOC-1 is required for cargo-specific sorting from vacuolar early endosomes toward lysosome-related organelles. Mol. Biol. Cell 18:768-780. Di Pietro, SM, JM Falcón-Pérez, D Tenza, SRG Setty, MS Marks, G Raposo and EC Dell'Angelica (2006) BLOC-1 interacts with BLOC-2 and the AP-3 complex to facilitate protein trafficking on endosomes. Mol. Biol. Cell 17:4027-4038. Theos, AC, JF Berson, SB Cromer, DC Harper, KE Herman, EV Sviderskaya, ML Lamoreux, DC Bennett, G Raposo and MS Marks (2006) Dual loss of ER export and endocytic signals with altered melanosome morphology in the silver mutation of Pmel17. Mol. Biol. Cell 17: 3598-3612. Theos, AC, ST Truschel, DC Harper, JF Berson, D Tenza, PC Thomas, G Raposo and MS Marks (2006) A novel pathway for sorting to intralumenal vesicles of multivesicular endosomes involved in organelle morphogenesis. Dev. Cell 10: 343-354 (see preview by Katzmann, DJ, 2006, Dev. Cell 10: 278-280 and Research Highlights by Smallridge, R, 2006, Nat. Rev. Mol. Cell Biol. 7:306-307). Fowler, DM, AV Koulov, C Alory-Jost, MS Marks, WE Balch and JW Kelly (2006) Functional amyloid formation within mammalian tissue. PLoS Biol. 4: e6. Theos, AC, D Tenza, JA Martina, I Hurbain, AA Peden, EV Sviderskaya, A Stewart, MS Robinson, DC Bennett, DF Cutler, JS Bonifacino, MS Marks and G Raposo (2005) Functions of AP-3 and AP-1 in tyrosinase sorting from endosomes to melanosomes. Mol. Biol. Cell. 16: 5356-5372. Yoshino, A, S.R.G. Setty, C. Poynton, A. St. Pol, E.L. Whiteman, C.G. Burd, E.L. Holzbaur, L. Johannes, J.M. McCaffery and M.S. Marks (2005) tGolgin-1 (p230, golgin-245) modulates Shiga toxin transport to the Golgi and Golgi motility toward the microtubule organizing centre. J Cell Sci. 118:2279-2293. |
