Signaling between cells and the uptake of macromolecular nutrients are mediated through cell surface receptors. Cellular mechanisms that control receptor trafficking through the endosomal compartment must be robust and act with high fidelity since failure to efficiently internalize or appropriately sort nutrient or signaling receptors can have dire consequences, ranging from heart disease to cancer. Research in the lab is directed toward understanding the mechanisms that govern receptor removal from the plasma membrane as well as their intracellular sorting and recycling. We employ a combination of genetic and mammalian cell-based assays to understand how nutrient and signaling receptor transport is controlled. To resolve the molecular details of how cells regulate receptor endocytosis and intracellular sorting, we complement cell-based assays with biochemical and combinatorial approaches.
Zheng L, Conner SD (2018) PI5P4Kγ functions in DTX1-mediated Notch signaling. Proc Natl Acad Sci U S A 115(9):1983–1990.
Zheng L, Conner SD (2017) Glycogen Synthase Kinase 3β Inhibition Enhances Notch1 Recycling. Mol Biol Cell 29(4):389–395.
Conner SD (2016) Regulation of Notch Signaling Through Intracellular Transport. International Review of Cell and Molecular Biology 323:107–127.
Shi B, Conner S, Liu J (2014) Dysfunction of Endocytic Kinase AAK1 in ALS. IJMS 15(12):22918–22932.
Waxmonsky N.C., and Conner S.D. (2013). αvβ3 integrin-mediated adhesion is regulated through an AAK1L- and EHD3-dependent rapid recycling pathway. J Cell Sci. 126, 3593-3601.
Zheng L., Saunders C.A., Sorensen E.B., Waxmonsky N.C., and Conner S.D. et al. (2013). Notch Signaling from the Endosome Requires a Conserved Di-Leucine Motif. Mol Biol Cell. 24, 297-307.
Kang Y.L., Yochem J., Bell L., Sorensen E.B., Chen L., and Conner S.D. et al. (2013). Caenorhabditis elegans Reveals a FxNPxY-Independent LDLR Internalization Mechanism Mediated by Epsin1. Mol Biol Cell. 24, 308-318.
Kuai L., Ong S.E., Madison J.M., Wang X., Duvall J.R., Lewis T.A., Luce C.J., Conner S.D., Pearlman D.A., JL, Schreiber S.L., SA et al. (2011). AAK1 Identified as an Inhibitor of Neuregulin-1/ ErbB4-Dependent Neurotrophic Factor Signaling Using Integrative Chemical Genomics and Proteomics. Chem & Biol. 18, 891-906.
Sorensen E.B., SD. (2010). γ secretase-dependent cleavage initiates Notch signaling from the plasma membrane. Traffic. 11, 1234-1245.
Sorensen, E.B. and Conner, S.D. (2008) AAK1 regulates Numb function at an early step in clathrin-mediated endocytosis. Traffic 9(10): 1791-1800
Henderson D.M., and Conner S.D. (2007). A novel AAK1 splice variant functions at multiple steps of the endocytic pathway. Mol Biol Cell. 18, 2698-2706.
Conner, S.D., and Schmid, S.L. (2003) Regulated Portals of Entry into the Cell. Nature. 422:37-44