Carol Otey, PhD
Associate Professor

Education:

BS Trinity University 1980
PhD University of California 1987

Mechanisms of Cell Motility and Adhesion

Many physiology processes depend upon the regulated movement of cells.  Examples include embryological morphogenesis, wound healing and targeting of immune cells to sites of infection.  However, when cell motility goes awry, this can result in serious pathologies.  The inappropriate movement of cancer cells during metastasis is one example; the movement of cells into the lumen of an artery during restenosis is another.   My lab studies the molecular basis of normal, regulated cell motility to understand how this fundamental process is controlled and how it is subverted to give rise to pathological situations.  We have focused on the actin cytoskeleton, which is largely responsible for establishing the shape of the cell and for controlling the changes in shape that occur when a cell crawls.  It is thought that rapid polymerization of actin at the cell’s leading edge is responsible for pushing the front of the cell forward, while actin microfilaments in the body of the cell simultaneously undergo contraction in order to pull the rest of the cell up. Our goal is to identify the molecular mechanisms that regulate both the protrusive assembly and the contractility of actin filaments.

	Figure 1. Palladin (in green) is concentrated in closely-spaced spots associated with contractile bundles of actin filaments (in red), in a cultured A7r5 vascular smooth muscle cell.
	(click to view larger image)

Currently, we are focusing much attention on a novel protein that was discovered in the Otey lab and named palladin.  Palladin has many features suggesting that it plays a critical role in regulating actin dynamics.   First, it closely co-localizes with actin-rich structures in a variety of cell types.  Second, it binds to a large number of proteins that are known to control actin assembly.  Third, its presence is required in order for a cell to maintain its actin cytoskeleton: when palladin expression is inhibited in a cultured cell, that cell’s cytoskeleton completely disassembles.  Conversely, when palladin is overexpressed in a cultured cell, this stimulates the formation of super-robust actin arrays.

Projects in the lab utilize a combination of biochemistry and molecular biology to explore palladin function in both cultured cell and animal models, using palladin as a unique tool to learn about mechanisms of cell motility.  Recently, we began investigating palladin’s role in the central nervous system, focusing on two different physiological processes: embryological development and response to injury.  Our results suggest that the motile ends of developing neurites (the growth cones) contain high concentrations of palladin.  If we inhibit palladin expression in embryonic neurons, they completely fail to extend their neurites, suggesting that the movement of a growth cone towards its target is highly dependent on palladin.  In the adult brain, palladin may play a central role in neuronal healing and re-extension of neurites following traumatic injury. Thus, we hope that palladin may provide us with a unique molecular tool that can be used to improve functional recovery of the central nervous system.

Recently, we and our collaborators have also begun to explore the function of palladin in other tissues. Palladin is upregulated during scar formation in the skin, as in the central nervous system, suggesting that it may have a conserved role in the response of organs to acute injury. Palladin also plays a key role in the response of vascular smooth muscle cells to stimulation by platelet-derived growth factor, so that palladin may be involved in the dynamic remodeling of the vasculature. Together, these results suggest that palladin may be an important player in cellular processes that depend upon the ability of cells to rapidly reorganize their actin cytoskeleton. Palladin is expressed in many different cell types and in all vertebrate species, so that a wide variety of cultured cell and animal models are available for exploring its function further.

Recent Publications:

Goicoechea, S., Disanza, A., Arneman, D., Scita, G. and Otey, C. (2006). Palladin binds to Eps8 and enhances dorsal ruffle and podosome formation. J. Cell Sci. 119:3316-24.

Rönty, M., Leivonen, S.K., Rachlin, A., Otey, C. and Carpén, O. (2006). Isoform-specific regulation of the actin-organizing protein palladin during TGF-β1-induced myofibroblast differentiation. J. Investigative Dermatology 126(11):2387-96.

Rachlin, A. and Otey, C. (2006) Identification of Palladin Isoforms and Characterization of an Isoform-specific Interaction between Lasp-1 and Palladin. J. Cell Sci. 119: 995-1004.

Boukhelifa, M., A. Rachlin, M.M. Parast, M. Moza, T. Johansson, O. Carpén, R. Karlsson and C.A. Otey. (2005) The proline-rich protein palladin binds directly to profilin. FEBS J. 273: 26-33.

Ronty, M., A. Taivainene, M. Moza, C.A. Otey and O. Carpén. (2004) Molecular analysis of the interaction between palladin and α-actinin. FEBS Lett. 566: 30-34.

Boukhelifa, M., M.M. Parast, J. Bear, F. Gertler and C.A. Otey. (2004) Palladin is a novel binding partner for Ena/VASP proteins. Cell Motil. Cytoskel. 58: 17-29.

Boukhelifa, M., S.-J. Hwang, J.G. Valtschanoff, R. Meeker, A. Rustioni and C. Otey. (2003) A critical role for palladin in astrocyte morphology and response to injury. Molec. Cell. Neuroscience 23: 661-668.

Rajfur, Z., P. Roy, C. Otey, L. Romer and K. Jacobson. (2002) The connection between stress fibers and focal adhesions: Dissecting the link employing chromophore assisted laser inactivation (CALI) with EGFP-fusion proteins. Nature Cell Biology 4: 286-293.

Boukhelifa, M., M.M. Parast, J.G. Valtschanoff, A.S. LaMantia, R.B. Meeker and C.A. Otey.  (2001) A role for the cytoskeletal protein palladin in neurite outgrowth. Molec. Biol. Cell 12: 2721-2729.

Hwang, S.J., Pagliardini S., Boukelifa M., Parast, M.M., Otey C.A., Rustioni A., Valtschanoff J.G.  (2001)  Palladin is expressed in excitatory terminals in the rat central nervous system. J. Comparative Neurol . 436: 211-224.

Parast, M.M. and C.A. Otey. (2000)  Characterization of palladin, a novel protein localized to stress fibers and cell adhesions. J. Cell Biol. 150 : 643-656.