Project 3 Angela Wandinger-Ness, PI Summary Receptor endocytosis is a fundamental cellular process that regulates the quality and duration of signal transduction. This project uses a systems-based approach to comparatively evaluate the endocytic trafficking of two receptors (FceRI immunoreceptor and the Epidermal Growth Factor Receptor, erbB1) in an immune cell line. The interdisciplinary team will test the hypothesis that ligand-dependent, receptor-specific signaling dictates spatial and temporal regulation of membrane trafficking machinery and pathway selection.
Three specific aims will examine how: 1) receptors are selectively internalized at the plasma membrane through clathrin-dependent and independent pathways;2) endocytic machinery responds to and is regulated by "input signals" from receptor cargo;and 3) receptor signaling is controlled by location and via specific interactions with endocytic proteins. Sophisticated spatiotemporal imaging will span nano to micron scales and will be integrated with biochemical analyses. The experimental data sets will iteratively inform rule-based mechanistic and population dynamics models. Outcomes from this research plan will reveal new information on pathway saturation limits, receptor competition for limiting components, among other parameters, that cannot be extrapolated when analyzing receptors individually.

Public Health Relevance

This project will take a systems biology approach to understand how two apparently distinct cellular processes - receptor endocytosis and receptor signaling - are linked in time and space. We expect to show that these processes are tightly coupled, orchestrating the cellular responses by feedback loops and interacting regulatory steps. Experimentalists on the team will use very innovative imaging methods to capture the sequences of events and the spatial relationships of players in both pathways. We will search for unknown players through targeted genetic screening and then validate these hits with novel microscopy and biochemical approaches. The large, complex data sets will be analyzed by mathematical modeling specialists. The interdisciplinary teams will work in coordinated fashion to use computation and bench skills to understand these very complex, inter-connected processes.

National Institute of Health (NIH)
Specialized Center (P50)
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Special Emphasis Panel (ZGM1)
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University of New Mexico Health Sciences Center
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Chylek, Lily A; Akimov, Vyacheslav; Dengjel, Jörn et al. (2014) Phosphorylation site dynamics of early T-cell receptor signaling. PLoS One 9:e104240
Chylek, Lily A; Harris, Leonard A; Tung, Chang-Shung et al. (2014) Rule-based modeling: a computational approach for studying biomolecular site dynamics in cell signaling systems. Wiley Interdiscip Rev Syst Biol Med 6:13-36
Wu, Meiye; Piccini, Matthew E; Singh, Anup K (2014) MiRNA detection at single-cell resolution using microfluidic LNA flow-FISH. Methods Mol Biol 1211:245-60
Itano, Michelle S; Graus, Matthew S; Pehlke, Carolyn et al. (2014) Super-resolution imaging of C-type lectin spatial rearrangement within the dendritic cell plasma membrane at fungal microbe contact sites. Front Phys 2:
Lund, Troy C; Patrinostro, Xiaobai; Kramer, Ashley C et al. (2014) sdf1 Expression reveals a source of perivascular-derived mesenchymal stem cells in zebrafish. Stem Cells 32:2767-79
Liu, Sheng; Lidke, Keith A (2014) A multiemitter localization comparison of 3D superresolution imaging modalities. Chemphyschem 15:696-704
Steinkamp, Mara P; Low-Nam, Shalini T; Yang, Shujie et al. (2014) erbB3 is an active tyrosine kinase capable of homo- and heterointeractions. Mol Cell Biol 34:965-77
Westrate, Laura M; Drocco, Jeffrey A; Martin, Katie R et al. (2014) Mitochondrial morphological features are associated with fission and fusion events. PLoS One 9:e95265
Valley, Christopher C; Lidke, Keith A; Lidke, Diane S (2014) The spatiotemporal organization of ErbB receptors: insights from microscopy. Cold Spring Harb Perspect Biol 6:
Jerman, Stephanie; Ward, Heather H; Lee, Rebecca et al. (2014) OFD1 and flotillins are integral components of a ciliary signaling protein complex organized by polycystins in renal epithelia and odontoblasts. PLoS One 9:e106330

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