We have been studying clathrin-independent forms of endocytosis (CIE) and have identified a number of endogenous PM proteins that enter cells through this mechanism. We have begun to study these proteins in detail in an attempt to understand how they travel in cells and whether they specifically interact with cellular machinery. We have identified signals in the cytoplasmic tails of CD44, CD98 and CD147 that are responsible for their altered trafficking and are looking for cellular machinery that is responsible for recognition and sorting of these signals. Understanding how these proteins move into and out of cells is important because these proteins are involved in interaction with the extracellular matrix (CD44), are involved in nutrient transport (CD98) and interact with integrins and matrix metalloproteinases (CD147). To facilitate these studies we are using SNAP-tag technology to quantify endocytosis and recycling of specific cell surface proteins. We are currently looking for compounds that inhibit or stimulate CIE. We have also been interested in examining the communication between CIE and clathrin-mediated endocytosis (CME). In examining the effects of Pitstop, a newly discovered inhibitor of CME, we found that it was also a potent inhibitor of CIE. Pitstop had been identified through a biochemical assay and although it does inhibit CME, it has broader effects.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2013
Total Cost
$592,635
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
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Donaldson, Julie G; Johnson, Debra L; Dutta, Dipannita (2016) Rab and Arf G Proteins in Endosomal Trafficking & Cell Surface Homeostasis. Small GTPases :0
Dutta, Dipannita; Donaldson, Julie G (2015) Sorting of Clathrin-Independent Cargo Proteins Depends on Rab35 Delivered by Clathrin-Mediated Endocytosis. Traffic 16:994-1009
Dutta, Dipannita; Donaldson, Julie G (2015) Rab and Arf G proteins in endosomal trafficking. Methods Cell Biol 130:127-38
Mayor, Satyajit; Parton, Robert G; Donaldson, Julie G (2014) Clathrin-independent pathways of endocytosis. Cold Spring Harb Perspect Biol 6:
Maldonado-Báez, Lymarie; Donaldson, Julie G (2013) Hook1, microtubules, and Rab22: mediators of selective sorting of clathrin-independent endocytic cargo proteins on endosomes. Bioarchitecture 3:141-6
Maldonado-Baez, Lymarie; Williamson, Chad; Donaldson, Julie G (2013) Clathrin-independent endocytosis: a cargo-centric view. Exp Cell Res 319:2759-69
Cole, Nelson B; Donaldson, Julie G (2012) Releasable SNAP-tag probes for studying endocytosis and recycling. ACS Chem Biol 7:464-9
Dutta, Dipannita; Williamson, Chad D; Cole, Nelson B et al. (2012) Pitstop 2 is a potent inhibitor of clathrin-independent endocytosis. PLoS One 7:e45799
Dutta, Dipannita; Donaldson, Julie G (2012) Search for inhibitors of endocytosis: Intended specificity and unintended consequences. Cell Logist 2:203-208
Rosemond, Erica; Rossi, Mario; McMillin, Sara M et al. (2011) Regulation of M₃ muscarinic receptor expression and function by transmembrane protein 147. Mol Pharmacol 79:251-61

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