Abstract

The proposal investigates the role of novel actin-binding proteins (espins) in the development and maintenance of hair bundle structure. The espins are an intriguing new family of Ca2+-insensitive actin-binding and bundling proteins found so far only in specialized cells such as intestinal brush border, Sertoli and hair cells. Family members differ in their N-termini, suggesting specialization of function. The proposed experiments will characterize actin-bundling of the isoforms in vitro, examine their effects on the actin cytoskeleton when transiently expressed in heterologous cell models, and look for molecular partners using the yeast 2-hybrid screen. Light and EM immunocytochemistry will be done to determine intracellular localization and how it changes with development. Finally, two genetic approaches will be taken to function: the anatomical and physiological effects of knocking out the espins will be examined, and the possibility that the jerker mouse mutant is an espin mutant will be investigated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC004314-02
Application #
6342370
Study Section
Special Emphasis Panel (ZRG1-IFCN-6 (01))
Program Officer
Freeman, Nancy
Project Start
2000-01-01
Project End
2002-12-31
Budget Start
2001-01-01
Budget End
2001-12-31
Support Year
2
Fiscal Year
2001
Total Cost
$322,464
Indirect Cost

  Institution

Name
Northwestern University at Chicago
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611

  Publications

Ahmed, Zubair M; Jaworek, Thomas J; Sarangdhar, Gowri N et al. (2018) Inframe deletion of human ESPN is associated with deafness, vestibulopathy and vision impairment. J Med Genet 55:479-488
Winkelman, Jonathan D; Suarez, Cristian; Hocky, Glen M et al. (2016) Fascin- and ?-Actinin-Bundled Networks Contain Intrinsic Structural Features that Drive Protein Sorting. Curr Biol 26:2697-2706
Zheng, Lili; Beeler, Dina M; Bartles, James R (2015) Characterization and regulation of an additional actin-filament-binding site in large isoforms of the stereocilia actin-bundling protein espin. J Cell Sci 128:2208
Zheng, Lili; Beeler, Dina M; Bartles, James R (2014) Characterization and regulation of an additional actin-filament-binding site in large isoforms of the stereocilia actin-bundling protein espin. J Cell Sci 127:1306-17
Sekerková, Gabriella; Richter, Claus-Peter; Bartles, James R (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:e1002032
Zheng, Lili; Zheng, Jing; Whitlon, Donna S et al. (2010) Targeting of the hair cell proteins cadherin 23, harmonin, myosin XVa, espin, and prestin in an epithelial cell model. J Neurosci 30:7187-201
Odeh, Hana; Hunker, Kristina L; Belyantseva, Inna A et al. (2010) Mutations in Grxcr1 are the basis for inner ear dysfunction in the pirouette mouse. Am J Hum Genet 86:148-60
Shin, Homin; Purdy Drew, Kirstin R; Bartles, James R et al. (2009) Cooperativity and frustration in protein-mediated parallel actin bundles. Phys Rev Lett 103:238102
Lieleg, Oliver; Schmoller, Kurt M; Purdy Drew, Kirstin R et al. (2009) Structural and viscoelastic properties of actin networks formed by espin or pathologically relevant espin mutants. Chemphyschem 10:2813-7
Sekerkova, Gabriella; Zheng, Lili; Mugnaini, Enrico et al. (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

Showing the most recent 10 out of 24 publications