Dr. Binks Wattenberg
Email Dr. Wattenberg
Phone Number: 502-852-7762
Lab Home Page
Area of Interest:Biological Membranes in Intracellular Signaling.
Laboratory Personnel:Brock, Stephanie Erin
My laboratory is engaged in two major projects, one involving the lipid signaling enzyme Sphingosine Kinase and the second to understand the trafficking and function of the so-called “Tail-Anchored” proteins.
Sphingosine-kinase: A Lipid Signalling Enzyme Sphingosine-phosphate has recently gained considerable attention as both an intracellular second messenger and an extracellular ligand for a novel group of receptors. Its signaling functions have been associated with a variety of critical cellular processes including cell survival and proliferation, cell migration, and expression of inflammatory adhesion molecules. The key regulatory step which determines levels of sphingosine-phosphate in the cell is the activity of sphingosine-kinase. Sphingosine-kinase activity is regulated by an interesting array of extracellular ligands including tumor necrosis factor, interleukin-1, and growth factors. Our recent studies have demonstrated that the signaling function of sphingosine kinase depends as much on where in the cell the enzyme is located as its degree of enzymatic activation. We are currently exploring how changes in localization of this critical signaling enzyme occur and why localization is such an important aspect of its signaling function.
Trafficking of Tail-Anchored Proteins. A substantial class of proteins are anchored by C-terminal membrane anchors to intracellular membranes. These are known as tail-anchored proteins. Prominent among these are the Bcl-2 family of apoptosis-related proteins, and the SNARE class of vesicle targeting proteins. Despite this importance, little is known about the mechanism that targets these proteins to their correct locations. The membrane anchor and flanking sequences also are responsible for targeting during membrane insertion and so are classified as signal/anchor sequences. The two known sites of insertion of these proteins are the endoplasmic reticulum and mitochondria. We have focused on the mechanism targeting these proteins to the mitochondrial outer membrane.We believe that the targeting of these proteins is the result of the interaction between a unique conformational structure of the signal/anchor sequences, molecular chaperones, and a membrane targeting and insertion apparatus in the mitochondrial outer membrane. We will are testing this hypothesis by determining the sequence and 3-dimensional structure of functional signal/anchors, identifying molecular chaperones that interact with those sequences, and identifying components of the mitochondrial targeting machinery.