James R. Bartles
Rank: Professor
Research area: Espin actin-bundling proteins, sensory neuroscience
Degree: Ph.D., Washington University
Voice: 312.503.1545
Fax: 312.503.7912
e-mail: j-bartles@northwestern.edu

Detailed research description:
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 of 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 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 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 Ca2+. In cells, espins efficiently elongate parallel actin bundles and, thereby, help determine the steady-state length of microvilli and stereocilia. Espins 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.

 

Representative publications:

Zheng, L., G. Sekerkova G, K. Vranich, L.G. Tilney, E. Mugnaini and J.R. Bartles (2000) The deaf jerker mouse has a mutation in the gene encoding the espin actin-bundling proteins of hair cell stereocilia and lacks espins. Cell 102, 377-385.

 

Loomis, P.A., L. Zheng, G. Sekerková, B. Changyaleket, E. Mugnaini, and J.R. Bartles (2003) Espin cross-links cause the elongation of microvillus-type parallel actin bundles in vivo.  J. Cell Biol. 163, 1045-1055.

 

Sekerková, G., L. Zheng, P.A. Loomis, B. Changyaleket, D.S. Whitlon, E. Mugnaini, and  J.R. Bartles (2004) Espins are multifunctional actin cytoskeletal regulatory proteins in the microvilli of chemosensory and mechanosensory cells.  J. Neurosci. 24, 5445-5456.

 

Sekerková, G., L. Zheng, E. Mugnaini, and J.R. Bartles (2006) Differential expression of espin isoforms during epithelial morphogenesis, stereociliogenesis and postnatal maturation in the developing inner ear.  Dev. Biol. 291, 83-95.

 

Loomis, P.A., A.E. Kelly, L. Zheng, B. Changyaleket, G. Sekerková, E. Mugnaini, A. Ferreira, R.D. Mullins, and J.R. Bartles (2006) Targeted wild-type and jerker espins reveal a novel, WH2 domain-dependent way to make actin bundles in cells.  J. Cell Sci.119, 1655-1665.

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