This project is focused on understanding clathrin-independent forms of endocytosis. Endocytosis that occurs without clathrin coats occurs in all cells but is poorly understood. We are interested in studying the cargo proteins that enter cells by this mechanism, their intracellular itinerary once they have been internalized and whether they contain amino acid sequences that allow for specialized sorting within cells. Recently we identified new cargo proteins that enter cells by this mechanism and have found that a subset of these new proteins take alternative traffic routes once they have entered cells. The major histocompatibility complex Class I protein (MHCI), is a prototypical clathrin-indepenent cargo protein and after internalization it reaches endosomes that contain cargo proteins such as the transferrin receptor that enter via clathrin-depenent endocytosis. From there, MHCI travels either to late endosomes and lysosomes where it is degraded or on to recycling tubules that return MHCI back to the cell surface. The new cargo proteins that we have identified (CD44, CD98, and CD147) show an altered itinerary in many cells where they traffic directly into the recycling tubules and avoid trafficking to late endosomal compartments. Consistent with this altered itinerary, we find that CD44, CD98 and CD147 are long-lived proteins and are not degraded like MHCI, which is routed to late endosomes. We recently showed that specific members of the MARCH family of E-3 ligases when expressed in cells target CD44 and CD98 for degradation.
| Zeltzer, Sebastian; Zeltzer, Carol A; Igarashi, Suzu et al. (2018) Virus Control of Trafficking from Sorting Endosomes. MBio 9: |
| Johnson, Debra L; Wayt, Jessica; Wilson, Jean M et al. (2017) Arf6 and Rab22 mediate T cell conjugate formation by regulating clathrin-independent endosomal membrane trafficking. J Cell Sci 130:2405-2415 |
| Donaldson, Julie G; Johnson, Debra L; Dutta, Dipannita (2016) Rab and Arf G Proteins in Endosomal Trafficking & Cell Surface Homeostasis. Small GTPases :0 |
| Donaldson, Julie G (2015) Immunofluorescence Staining. Curr Protoc Cell Biol 69:4.3.1-7 |
| Funakoshi, Yuji; Chou, Margaret M; Kanaho, Yasunori et al. (2014) TRE17/USP6 regulates ubiquitylation and trafficking of cargo proteins that enter cells by clathrin-independent endocytosis. J Cell Sci 127:4750-61 |
| Karabasheva, Darya; Cole, Nelson B; Donaldson, Julie G (2014) Roles for trafficking and O-linked glycosylation in the turnover of model cell surface proteins. J Biol Chem 289:19477-90 |
| Porat-Shliom, Natalie; Weigert, Roberto; Donaldson, Julie G (2013) Endosomes derived from clathrin-independent endocytosis serve as precursors for endothelial lumen formation. PLoS One 8:e81987 |
| Maldonado-Báez, Lymarie; Williamson, Chad; Donaldson, Julie G (2013) Clathrin-independent endocytosis: a cargo-centric view. Exp Cell Res 319:2759-69 |
| Maldonado-Báez, Lymarie; Cole, Nelson B; Krämer, Helmut et al. (2013) Microtubule-dependent endosomal sorting of clathrin-independent cargo by Hook1. J Cell Biol 201:233-47 |
| Rosemond, Erica; Rossi, Mario; McMillin, Sara M et al. (2011) Regulation of M? muscarinic receptor expression and function by transmembrane protein 147. Mol Pharmacol 79:251-61 |
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