William Schilling

Professor

Ph.D., South Carolina at Charleston, 1981
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Structure, Function, and Regulation of Mammalian TRPC Channels

RESEARCH DESCRIPTION

The long range goal of my research is to understand the molecular mechanisms associated with agonist-induced Ca2+ signaling in mammalian non-excitable cells and in particular, in vascular endothelial cells and renal epithelial cells. TRP genes, originally identified as critical components of phototransduction in Drosophila, encode a ubiquitous and heterogeneous family of ion channel proteins that appear to play a fundamental role in Ca2+ signaling. In the last six years more than 20 mammalian homologs have been discovered. There are currently seven mammalian TRP siblings designated TRPC1-TRPC7, which exhibit ~38% overall identity at the amino acid level to the Drosophila isoforms. The primary TRPC channels, like the Drosophila versions, appear to be regulated by phospholipase C-dependent mechanisms and are thus, intimately involved in receptor-mediated Ca2+ signaling. In many cell types, a specific receptor-activated channel appears to be regulated by the level of Ca2+ within the Ins(1,4,5)P3-sensitive internal Ca2+ store. These so-called store-operated channels (SOCs) are responsible for the sustained elevation in cytosolic Ca2+ observed following receptor stimulation and there is growing evidence that the primary TRPCs are SOCs. Taking a proteomics approach, our research focus is on understanding the structure, function and regulation of mammalian TRPC channels, their targeting and localization to specific membrane domains and subcellular compartments, and their physical interaction with other proteins involved in a variety of signal transduction cascades important for cell proliferation, migration, and development. Through the combination of sophisticated imaging techniques and immunocytochemical approaches, coupled with protein structural analysis, we hope to identify novel signaling complexes that play an important role in normal cellular physiology and in the development and progression of specific disease states.

RELATED RESEARCH AREAS

View William Schilling's Publications on PubMed