QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, June 14, 2006, 26(24):6543-6553; doi:10.1523/JNEUROSCI.0693-06.2006

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (39) Citing Articles via Google Scholar Google Scholar Articles by McGee, J. Articles by Richardson, G. P. Search for Related Content PubMed PubMed Citation Articles by McGee, J. Articles by Richardson, G. P.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
The Very Large G-Protein-Coupled Receptor VLGR1: A Component of the Ankle Link Complex Required for the Normal Development of Auditory Hair Bundles

JoAnn McGee,^1 * Richard J. Goodyear,^2 * D. Randy McMillan,^3 * Eric A. Stauffer,⁴ Jeffrey R. Holt,⁴ Kirsten G. Locke,⁵ David G. Birch,⁵ P. Kevin Legan,² Perrin C. White,³ Edward J. Walsh,¹ and Guy P. Richardson²

¹Developmental Auditory Physiology Laboratory, Boys Town National Research Hospital, Omaha, Nebraska 68131, ²School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, United Kingdom, ³Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9063, ⁴Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, Virginia 22908, and ⁵Retina Foundation of the Southwest, Dallas, Texas 75225

Correspondence should be addressed to Dr. Perrin C. White, Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9063. Email: perrin.white{at}utsouthwestern.edu

Sensory hair bundles in the inner ear are composed of stereocilia that can be interconnected by a variety of different link types, including tip links, horizontal top connectors, shaft connectors, and ankle links. The ankle link antigen is an epitope specifically associated with ankle links and the calycal processes of photoreceptors in chicks. Mass spectrometry and immunoblotting were used to identify this antigen as the avian ortholog of the very large G-protein-coupled receptor VLGR1, the product of the Usher syndrome USH2C (Mass1) locus. Like ankle links, Vlgr1 is expressed transiently around the base of developing hair bundles in mice. Ankle links fail to form in the cochleae of mice carrying a targeted mutation in Vlgr1 (Vlgr1/del7TM), and the bundles become disorganized just after birth. FM1-43 [N-(3-triethylammonium)propyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide] dye loading and whole-cell recordings indicate mechanotransduction is impaired in cochlear, but not vestibular, hair cells of early postnatal Vlgr1/del7TM mutant mice. Auditory brainstem recordings and distortion product measurements indicate that these mice are severely deaf by the third week of life. Hair cells from the basal half of the cochlea are lost in 2-month-old Vlgr1/del7TM mice, and retinal function is mildly abnormal in aged mutants. Our results indicate that Vlgr1 is required for formation of the ankle link complex and the normal development of cochlear hair bundles.

Key words: cochlea; hair cell; Usher syndrome; knock-out mice; GPCR; retina

---

Received Feb. 16, 2006; revised May 1, 2006; accepted May 2, 2006.

Correspondence should be addressed to Dr. Perrin C. White, Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9063. Email: perrin.white{at}utsouthwestern.edu

This article has been cited by other articles:

				R. Geng, S. F. Geller, T. Hayashi, C. A. Ray, T. A. Reh, O. Bermingham-McDonogh, S. M. Jones, C. G. Wright, S. Melki, Y. Imanishi, et al. Usher syndrome IIIA gene clarin-1 is essential for hair cell function and associated neural activation Hum. Mol. Genet., August 1, 2009; 18(15): 2748 - 2760. [Abstract] [Full Text] [PDF]

				G. Tian, Y. Zhou, D. Hajkova, M. Miyagi, A. Dinculescu, W. W. Hauswirth, K. Palczewski, R. Geng, K. N. Alagramam, J. Isosomppi, et al. Clarin-1, Encoded by the Usher Syndrome III Causative Gene, Forms a Membranous Microdomain: POSSIBLE ROLE OF CLARIN-1 IN ORGANIZING THE ACTIN CYTOSKELETON J. Biol. Chem., July 10, 2009; 284(28): 18980 - 18993. [Abstract] [Full Text] [PDF]

				I. A. Belyantseva, B. J. Perrin, K. J. Sonnemann, M. Zhu, R. Stepanyan, J. McGee, G. I. Frolenkov, E. J. Walsh, K. H. Friderici, T. B. Friedman, et al. {gamma}-Actin is required for cytoskeletal maintenance but not development PNAS, June 16, 2009; 106(24): 9703 - 9708. [Abstract] [Full Text] [PDF]

				L. Pan, J. Yan, L. Wu, and M. Zhang Assembling stable hair cell tip link complex via multidentate interactions between harmonin and cadherin 23 PNAS, April 7, 2009; 106(14): 5575 - 5580. [Abstract] [Full Text] [PDF]

				R. Stepanyan and G. I. Frolenkov Fast Adaptation and Ca2+ Sensitivity of the Mechanotransducer Require Myosin-XVa in Inner But Not Outer Cochlear Hair Cells J. Neurosci., April 1, 2009; 29(13): 4023 - 4034. [Abstract] [Full Text] [PDF]

				N Hilgert, K Kahrizi, N Dieltjens, N Bazazzadegan, H Najmabadi, R J H Smith, and G Van Camp A large deletion in GPR98 causes type IIC Usher syndrome in male and female members of an Iranian family J. Med. Genet., April 1, 2009; 46(4): 272 - 276. [Abstract] [Full Text] [PDF]

				A. F. J. van Aken, M. Atiba-Davies, W. Marcotti, R. J. Goodyear, J. E. Bryant, G. P. Richardson, K. Noben-Trauth, and C. J. Kros TRPML3 mutations cause impaired mechano-electrical transduction and depolarization by an inward-rectifier cation current in auditory hair cells of varitint-waddler mice J. Physiol., November 15, 2008; 586(22): 5403 - 5418. [Abstract] [Full Text] [PDF]

				T. Maerker, E. van Wijk, N. Overlack, F. F.J. Kersten, J. McGee, T. Goldmann, E. Sehn, R. Roepman, E. J. Walsh, H. Kremer, et al. A novel Usher protein network at the periciliary reloading point between molecular transport machineries in vertebrate photoreceptor cells Hum. Mol. Genet., January 1, 2008; 17(1): 71 - 86. [Abstract] [Full Text] [PDF]

				N. Michalski, V. Michel, A. Bahloul, G. Lefevre, J. Barral, H. Yagi, S. Chardenoux, D. Weil, P. Martin, J.-P. Hardelin, et al. Molecular Characterization of the Ankle-Link Complex in Cochlear Hair Cells and Its Role in the Hair Bundle Functioning J. Neurosci., June 13, 2007; 27(24): 6478 - 6488. [Abstract] [Full Text] [PDF]

				X. Liu, O. V. Bulgakov, K. N. Darrow, B. Pawlyk, M. Adamian, M. C. Liberman, and T. Li Usherin is required for maintenance of retinal photoreceptors and normal development of cochlear hair cells PNAS, March 13, 2007; 104(11): 4413 - 4418. [Abstract] [Full Text] [PDF]

				M. Schwander, A. Sczaniecka, N. Grillet, J. S. Bailey, M. Avenarius, H. Najmabadi, B. M. Steffy, G. C. Federe, E. A. Lagler, R. Banan, et al. A Forward Genetics Screen in Mice Identifies Recessive Deafness Traits and Reveals That Pejvakin Is Essential for Outer Hair Cell Function J. Neurosci., February 28, 2007; 27(9): 2163 - 2175. [Abstract] [Full Text] [PDF]

				H. Yagi, H. Tokano, M. Maeda, T. Takabayashi, T. Nagano, H. Kiyama, S. Fujieda, K. Kitamura, and M. Sato Vlgr1 is required for proper stereocilia maturation of cochlear hair cells. Genes Cells, February 1, 2007; 12(2): 235 - 250. [Abstract] [Full Text] [PDF]

				H. Kremer, E. van Wijk, T. Marker, U. Wolfrum, and R. Roepman Usher syndrome: molecular links of pathogenesis, proteins and pathways Hum. Mol. Genet., October 15, 2006; 15(suppl_2): R262 - R270. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help