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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, which are specialized structures found only in certain cell types. Our major model system is the pigment organelle in melanocytes, the melanosome, but we are developing additional models in platelets / megakaryocytes and dendritic cells of the immune system. These organelles provide useful models for understanding how genetic diseases alter sorting processes required for organelle formation and subsequent physiological function. 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. Selected Publications: Sitaram, A, R Piccirillo, I Palmisano, DC Harper, EC Dell'Angelica, MV Schiaffino and MS Marks (2009). Localization to mature melanosomes by virtue of cytoplasmic dileucine motifs is required for human OCA2 function. Mol. Biol. Cell. 20:1464-1477. Hurbain, I, WJC Geerts, T Boudier, S Marco, AJ Verkleij, MS Marks and G Raposo (2008) Electron tomography of early melanosomes: implications for melanogenesis and the generation of fibrillar amyloid sheets. Proc. Natl. Acad. Sci. U.S.A. 105:19726-19731. Setty, SRG, D Tenza, EV Sviderskaya, DC Bennett, G Raposo and MS Marks (2008) Cell-specific ATP7A transport sustains copper-dependent tyrosinase activity in melanosomes. Nature 454:1142-1146. 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. 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. |
