Henry F. Epstein, M.D.
Professor
Cecil H. and Ida Green Distinguished
University Chair
Professor and
Chair, Department of Neuroscience and Cell Biology
Telephone: (409) 772-2751
Fax: (409) 772-3381
E-mail: hepstein@utmb.edu
Campus Location: 120G Basic Science Bldg.
Mail Route: 0625
Research
The Cytoskeleton in Nerve and Muscle
The current focus of Dr. Epstein's laboratory is on characterizing novel proteins regulating the cytoskeleton. Genetic analysis is now turning to mouse lines as well as Caenorhabditis elegans to facilitate medical applications.
Biochemical and genetic studies on the C. elegans model as well as in various fungal species have demonstrated that a novel molecular chaperone is required for the proper folding, assembly, and function of myosins and myosin-like protein motors. The chaperone protein, named UNC-45 after the canonical gene in C. elegans, binds the well-known molecular chaperone Hsp90 as well as myosin. In mice and humans, two UNC-45-like genes are present and encode closely related but distinct isoforms. One isoform is present in many cell types and appears necessary for cell division and membrane fusion; the other isoform is expressed predominantly in heart and skeletal muscle and is necessry for sarcomere organization. The UNC-45 mammalian homologues may prove to be important targets for genetic and pharmacological intervention in certain cancers and heart failure.
Dr. Epstein's laboratory was part of the international consortium that cloned and identified the myotonic dystrophy locus. The major protein product of that locus, myotonic dystrophy protein kinase (DMPK), is a serine-threonine protein kinase related to Rho kinase and other regulators of cell cycle, cytoskeletal, and membrane-associated processes. DMPK appears to team up with Rho kinase and myosin light chain kinase (MLCK) to regulate the assembly and function of myosin and the actin cytoskeleton. The membrane-associated regulators Rac-1 and Raf-1 activate DMPK whereas the cytosolic RhoA activates Rho kinase. DMPK and negative regulator of cytoskeletal myosin II. Our hypothesis is that DMPK along with MLCK activates the membrane-associated cytoskeleton whereas Rho kinase activates the cytosolic system. The DMPK system may be particularly important in the development and function of highly plastic synapses related to learning and memory of the brain.