Cells that help the body to defend itself against infection, such as leukocytes, are guided to the site of a wound or infection by chemical cues (a process known as chemotaxis) released by the affected tissue. Metastatic cancer cells can also move out from the site of a primary tumor towards blood vessels by the same chemotactic process, resulting in the spread of cancer. Both of these cell types move rapidly, using a specialized form of motility referred to as “amoeboid”. This type of motility is characterized by extension of pseudopodia in the front of the cell, in the direction of movement, that is followed by contraction of the rear of the cell. Amoeboid cells make specific contact with surrounding substrates, but they form weak, broad adhesions that allows them to rapidly break these contacts, enabling rapid movement.
The overall goal of the research in the Titus laboratory is to understand how the actin cytoskeleton and its associated motors, myosins, and actin binding proteins that link the cytoskeleton to adhesion receptors are used to generate amoeboid motility and how cells interpret extracellular cues to move directionally. Our model organism of choice is the social amoebae Dictyostelium discoideum, a powerful experimental system that has a well-characterized actin cytoskeleton, a robust chemotactic response and is amenable to a wide range of experimental approaches, including molecular genetic, cell biological and biochemical methods.
Selected Publications (Pubmed Search)
Klein, J.C., Burr, A.R., Svensson, B., Kennedy, D.J., Titus, M.A., Rayment, I.,& Thomas, D.D. (2008). Actin-binding cleft closure in myosin II probed by site-directed spin labeling and pulsed EPR. P.N.A.S. 105:12867-12872
Agafonov, R.V, Titus, M.A., Thomas, D.D. & Nesmelov, Y.E. (2008). Muscle and nonmuscle myosins probed by a spin label at equivalent sites in the force-generating domain. P.N.A.S. 105:13397-13402
Wang Q., Deloia M.A., Kang Y., Litchke C., Zhang, N., Titus M.A., & Walters, K.J. (2007). The SH3 domain of a M7 interacts with its C-terminal proline rich region. Prot. Sci. 16:189-196
Mini-Review - Titus, M.A. (2006). Myosin I and actin dynamics: the frogs weigh in. Dev. Cell 11:594-595
Titus MA (2005) An unexpected role for myosins in adhesion. Novartis Foundation Symposium Proceedings, in press.
Titus MA (2004) Myosins meet microtubules. Nature 431:252-253.
Titus MA (2004) The role of talin and myosin VII in adhesion - A FERM connection. in: Cell Motility. From molecules to organisms., A. Ridley, M Peckham & P. Clark, eds. pp 19-37.
Cooper JA and Titus MA. co-editors, Curr.Op. Cell Biol. - Cell Structure & Dynamics Issue for 2004 (volume 16, pages 1-112).
Falk DL, Wessels D, Jenkins L, Pham T, Kuhl S, Titus MS, and Soll DR (2003) Shared, unique and redundant functions of three myosin Is (myoA, myoB and myoF) in motility and chemotaxis in Dictyostelium. J. Cell Sci. 116:3985-3999