Duggan, Anne, PhD



Duggan, Anne, PhD





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Ward 10-070 Chicago

Areas of Research

Molecular Neuroscience, Signal Transduction

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Current Research

Current Research

The DEG/ENaC family comprises a large group of two-transmembrane domain proteins which form amiloride-sensitive sodium channels that have been implicated in responses to touch, extracellular protons, and neuropeptides. My research, performed in collaboration with Jaime Garc’a-A–overos, focuses on the BNaC/ASIC subfamily, formed by six mammalian neuronal sodium channels that are not gated by voltage but may be activated by extracellular protons and have thus been proposed to mediate some forms of acid-induced pain.
Furthermore, one BNaC/ASIC channel – BNaC1 – localizes to the mechanosensory terminals of mammalian dorsal root and trigeminal ganglia neurons, and is necessary for normal touch sensitivity. In addition, some BNaC/ASIC channels are expressed by brain neurons and some localize to dendrites, suggesting roles for these acid-gated channels in the neuronal response to ischemia and in synaptic transmission.
Our approach to the study of these channels and their roles in the central and peripheral nervous systems is to identify interacting proteins using molecular and biochemical methods such as yeast two-hybrid screens and co-immunoprecipitations from neuronal tissue. These methods have been used in the study of other channels to identify proteins that are involved in channel function, localization, anchoring to the cytoskeleton and the extracellular matrix, and trafficking to and from the cell surface.
Using a two-hybrid screen, we have identified a PDZ domain protein, PICK1, which binds to the C-terminus of BNaC1. PICK1 is expressed in DRG neurons and localizes at mechanosensory terminals with BNaC1. We plan to investigate the role of PICK1 in BNaC1 function using mice with mutations in each gene. We intend to screen DRG libraries for additional interactors. In parallel, we plan to use biochemical (immunoprecipitations) and genomic (GeneChip) approaches to identify other proteins that interact with BNaC/ASIC channels, with the ultimate goal of revealing the macromolecular components of these channel complexes.