Selwyn A. Williams
» Pearl 313 (P-313)
Dissecting the mechanism of adhesion modulation of fibronectin
The overall goal of my current research is to provide further insight into how the extracellular matrix (ECM) protein fibronectin (FN), regulates cell morphology and function in physiological and pathological processes. The ECM is an extensive, fibrillar network with fibronectin as a major structural and functional component. Fibronectin is a dimeric, ubiquitously expressed glycoprotein that plays key roles in cellular processes such as adhesion, spreading and migration, hemostasis and thrombosis, proliferation and differentiation, cell morphology and oncogenic transformation. Fibronectin controls many cellular events through direct, coordinated interactions with other ECM components and with integrin cell surface receptors. Modification of cell interactions with fibronectin occurs through the actions of adhesion-modulatory proteins, a structurally diverse group that includes tenascin-C, fibulin-1, thrombospondin-1, and others. Adhesion modulation defines a particular subset of ECM interactions in which modulatory proteins confer anti-adhesive properties to the ECM. By reducing cell-ECM interactions, these modulatory proteins alter cell behavior and morphology and provide conditions conducive to cell migration, proliferation, and other cell activities important during tissue repair and remodeling. Our research seeks to understand the mechanisms by which disparate adhesion modulatory proteins alter the properties of the fibronectin matrix.
Unconventional myosin function in Tetrahymena thermophila.
Myosins are ubiquitous molecular motors that catalyze an ATP-dependent interaction with actin filaments and generate unidirectional chemo-mechanical force. Over 18 classes of myosins have been identified within diverse taxa, however functional designations to these classes have been lagging significantly. Our initial studies reported the function of MYO1, a novel, unconventional myosin first identified in the ciliate Tetrahymena thermophila. Using gene knockout technology to create a MYO1-null strain, we were able to determine a role for MYO1 in nuclear positioning and elongation during cell division, and in phagocytosis. Subsequently, we have identified 12 additional myosins genes in Tetrahymena comprising a new subgroup of class XIV myosins. The functions of these new myosin members are unknown, and an integral part of my research is to identify their possible roles in cellular processes. Tetrahymena's myosins possess structural complexity comparable to some classes of vertebrae myosins and can be a useful model in understanding the domain-specific interactions among myosins and other intracellular actors. These studies may provide a broader understanding of how myosins and their structural components function in higher eukaryotes.