James R. Bartles

Rank: Professor

Research area: Espin actin-bundling proteins, hair cell stereocilia, the actin cytoskeleton of sensory and neuronal cells

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 actin-bundling proteins, and the elucidation of their roles in the stereocilia of sensory hair cells in the inner ear. Espins are produced in multiple isoforms from a single gene. They are present at high concentration in the parallel actin bundle scaffold at the core of hair cell stereocilia and are the target of deafness mutations in mice and humans. For example, the jerker mutation in the mouse espin gene causes recessive hereditary deafness and vestibular dysfunction and results in malformed hair cell stereocilia, which are abnormally short and thin. Beyond hair cell stereocilia, espins are present at high concentration in the microvillus-based specializations of other sensory cells (taste receptor cells, solitary chemoreceptor cells, vomeronasal sensory neurons and Merkel cells) and in the dendritic spines of cerebellar Purkinje cells, suggesting that the proteins also play important roles in the F-actin-rich specializations of other sensory and neuronal cells. Espins show no obvious sequence similarities to other confirmed actin-bundling proteins, but show limited sequence homology to the forked proteins of Drosophila. Espins differ from most other actin-bundling proteins in that they bind F-actin with high affinity, exert a potent cooperative effect on the twist of actin filaments in parallel actin bundles, and are not inhibited by Ca2+. In cells, espins bring about the elongation of parallel actin bundles and, thereby, help to determine the steady-state length of structures like stereocilia and microvilli. In fact, heterologous expression of espins in epithelial cell lines causes a dramatic elongation of microvilli to produce stereocilium facsimiles suitable for reconstitution studies. Espins also bind actin monomer via their Wiskott-Aldrich Syndrome protein homology 2 (WH2) domain and can assemble actin bundles in cells. Certain espin isoforms can also bind phosphatidylinositol 4,5-bisphosphate, profilins or SH3 proteins. This constellation of biological activities may make espins especially well-suited for regulating the actin cytoskeleton in sensory and neuronal cells.

 

 

Representative publications:

 

Zheng, L., G. Sekerková 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.

 

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.

 

Purdy, K.R., J.R. Bartles, and G.C. Wong (2007) Structural polymorphism of the actin-espin system: a prototypical system of filaments and linkers in stereocilia. Phys. Rev. Lett. 98, 058105.

 

Sekerková, G., L. Zheng, E. Mugnaini, and J.R. Bartles (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, 661-676.

 

Shin, H., K.R. Purdy Drew, J.R. Bartles, G.C. Wong, and G.M. Grason (2009) Cooperativity and frustration in protein-mediated parallel actin bundles. Phys. Rev. Lett. 103, 238102.

 

Zheng, L., J. Zheng, D.S. Whitlon, J. García-Añoveros, and J.R. Bartles (2010) Targeting of the hair cell proteins cadherin 23, harmonin, myosin XVa, espin, and prestin in an epithelial cell model. J. Neurosci. 30, 7187-7201. 

 

Sekerková, G., C.-P. Richter, and J.R. Bartles (2011) Roles of the espin actin-bundling proteins in the morphogenesis and stabilization of hair cell stereocilia revealed in CBA/CaJ congenic jerker mice. PLoS Genet. 7(3): e1002032.