James Richard Bartles, PhD
Professor of Cell and Molecular Biology
Feinberg School of Medicine
Research Interests:
The research in my lab is centered on the “espins”, a novel family of multifunctional actin-bundling proteins, and the elucidation of their roles in the organization and function of the actin cytoskeleton in hair cell stereocilia and sensory cell microvilli. Espins are produced in multiple isoforms from a single gene. They are present at high concentration in the parallel actin bundle of hair cell stereocilia and are the target of multiple deafness mutations in mice and humans. For example, the jerker mutation in mice causes recessive hereditary deafness and vestibular dysfunction accompanied by an abnormal shortening and thinning of hair cell stereocilia. Espins are also present at high concentration in the microvilli of taste receptor cells, solitary chemoreceptor cells, vomeronasal sensory neurons and Merkel cells, suggesting that these proteins play important, general roles in the microvillar projections of vertebrate sensory cells. Unlike other actin-bundling proteins found in the microvilli and stereocilia of vertebrates, espins are potent actin-bundling proteins that are not inhibited by calcium ion. In cells, espins efficiently elongate parallel actin bundles and, thereby, help determine the steady-state length of microvilli and stereocilia. Espins also bind actin monomer via their Wiskott-Aldrich Syndrome protein homology 2 (WH2) domain in vitro and in vivo and can assemble actin bundles in cells. Certain espin isoforms can also bind phosphatidylinositol 4,5-bisphosphate, profilins or SH3 proteins. These biological activities distinguish espins from other actin-bundling proteins and may make them especially well-suited to sensory cells.
Selected Publications:
Nagata, K., Zheng, L., Madathany, T., Castiglioni, A. J., Bartles, J. R. and Garcia-Anoveros, J. (2008). The varitint-waddler (Va) deafness mutation in TRPML3 generates constitutive, inward rectifying currents and causes cell degeneration. Proc Natl Acad Sci U S A 105, 353-8.
Sekerkova, G., Zheng, L., Mugnaini, E. and Bartles, J. R. (2008). Espin actin-cytoskeletal proteins are in rat type I spiral ganglion neurons and include splice-isoforms with a functional nuclear localization signal. J Comp Neurol 509, 661-76.
Loomis, P. A., Kelly, A. E., Zheng, L., Changyaleket, B., Sekerkova, G., Mugnaini, E., Ferreira, A., Mullins, R. D. and Bartles, J. R. (2006). Targeted wild-type and jerker espins reveal a novel, WH2-domain-dependent way to make actin bundles in cells. J Cell Sci 119, 1655-65.
Sekerkova, G., Zheng, L., Mugnaini, E. and Bartles, J. R. (2006). Differential expression of espin isoforms during epithelial morphogenesis, stereociliogenesis and postnatal maturation in the developing inner ear. Dev Biol 291, 83-95.
Sekerkova, G., Zheng, L., Loomis, P. A., Changyaleket, B., Whitlon, D. S., Mugnaini, E. and Bartles, J. R. (2004). Espins are multifunctional actin cytoskeletal regulatory proteins in the microvilli of chemosensory and mechanosensory cells. J Neurosci 24, 5445-56.
