Human Molecular Genetics Advance Access originally published online on December 8, 2004
Human Molecular Genetics 2005 14(3):347-356; doi:10.1093/hmg/ddi031
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Human Molecular Genetics, Vol. 14, No. 3 © Oxford University Press 2005; all rights reserved
Interactions in the network of Usher syndrome type 1 proteins
1Unité de Génétique des Déficits Sensoriels, INSERM U587, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris cedex 15, France, 2Department of Laboratory Animal Science, The Tokyo Metropolitan Institute of Medical Science (Rinshoken), Tokyo, Japan, 3Institute of Zoology, University of Mainz, Germany and 4Department of Otolaryngology-HNS, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, OH, USA
* To whom correspondence should be addressed. Tel: +33 1456888 90/93; Fax: +33 145676978; Email: cpetit{at}pasteur.fr
Received September 28, 2004; Revised November 7, 2004; Accepted November 25, 2004
Defects in myosin VIIa, harmonin (a PDZ domain protein), cadherin 23, protocadherin 15 and sans (a putative scaffolding protein), underlie five forms of Usher syndrome type I (USH1). Mouse mutants for all these proteins exhibit disorganization of their hair bundle, which is the mechanotransduction receptive structure of the inner ear sensory cells, the cochlear and vestibular hair cells. We have previously demonstrated that harmonin interacts with cadherin 23 and myosin VIIa. Here we address the extent of interactions between the five known USH1 proteins. We establish the previously suggested sans–harmonin interaction and find that sans also binds to myosin VIIa. We show that sans can form homomeric structures and that harmonin b can interact with all harmonin isoforms. We reveal that harmonin also binds to protocadherin 15. Molecular characterization of these interactions indicates that through its binding to four of the five USH1 proteins, the first PDZ domain (PDZ1) of harmonin plays a central role in this network. We localize sans in the apical region of cochlear and vestibular hair cell bodies underneath the cuticular plate. In contrast to the other four known USH1 proteins, no sans labeling was detected within the stereocilia. We propose that via its binding to myosin VIIa and/or harmonin, sans controls the hair bundle cohesion and proper development by regulating the traffic of USH1 proteins en route to the stereocilia.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. Lefevre, V. Michel, D. Weil, L. Lepelletier, E. Bizard, U. Wolfrum, J.-P. Hardelin, and C. Petit A core cochlear phenotype in USH1 mouse mutants implicates fibrous links of the hair bundle in its cohesion, orientation and differential growth Development, April 15, 2008; 135(8): 1427 - 1437. [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]
|
|
|
|
 |
|
 V. Hyenne, J. C Harf, M. Latz, B. Maro, U. Wolfrum, and M.-C. Simmler Vezatin, a ubiquitous protein of adherens cell-cell junctions, is exclusively expressed in germ cells in mouse testis Reproduction, March 1, 2007; 133(3): 563 - 574. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T Jaijo, E Aller, M Beneyto, C Najera, C Graziano, D Turchetti, M Seri, C Ayuso, M Baiget, F Moreno, et al. MYO7A mutation screening in Usher syndrome type I patients from diverse origins J. Med. Genet., March 1, 2007; 44(3): e71 - e71. [Full Text] [PDF]
|
|
|
|
|
|
F. P M Cremers, W. J Kimberling, M. Kulm, A. P de Brouwer, E. van Wijk, H. te Brinke, C. W R J Cremers, L. H Hoefsloot, S. Banfi, F. Simonelli, et al. Development of a genotyping microarray for Usher syndrome J. Med. Genet., February 1, 2007; 44(2): 153 - 160. [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]
|
|
|
|
|
|
Z. M. Ahmed, R. Goodyear, S. Riazuddin, A. Lagziel, P. K. Legan, M. Behra, S. M. Burgess, K. S. Lilley, E. R. Wilcox, S. Riazuddin, et al. The tip-link antigen, a protein associated with the transduction complex of sensory hair cells, is protocadherin-15. J. Neurosci., June 28, 2006; 26(26): 7022 - 7034. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Grati, M. E. Schneider, K. Lipkow, E. E. Strehler, R. J. Wenthold, and B. Kachar Rapid turnover of stereocilia membrane proteins: evidence from the trafficking and mobility of plasma membrane Ca(2+)-ATPase 2. J. Neurosci., June 7, 2006; 26(23): 6386 - 6395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. van Wijk, B. van der Zwaag, T. Peters, U. Zimmermann, H. te Brinke, F. F.J. Kersten, T. Marker, E. Aller, L. H. Hoefsloot, C. W.R.J. Cremers, et al. The DFNB31 gene product whirlin connects to the Usher protein network in the cochlea and retina by direct association with USH2A and VLGR1 Hum. Mol. Genet., March 1, 2006; 15(5): 751 - 765. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Senften, M. Schwander, P. Kazmierczak, C. Lillo, J.-B. Shin, T. Hasson, G. S. G. Geleoc, P. G. Gillespie, D. Williams, J. R. Holt, et al. Physical and Functional Interaction between Protocadherin 15 and Myosin VIIa in Mechanosensory Hair Cells J. Neurosci., February 15, 2006; 26(7): 2060 - 2071. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Adato, G. Lefevre, B. Delprat, V. Michel, N. Michalski, S. Chardenoux, D. Weil, A. El-Amraoui, and C. Petit Usherin, the defective protein in Usher syndrome type IIA, is likely to be a component of interstereocilia ankle links in the inner ear sensory cells Hum. Mol. Genet., December 15, 2005; 14(24): 3921 - 3932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Reiners, E. van Wijk, T. Marker, U. Zimmermann, K. Jurgens, H. te Brinke, N. Overlack, R. Roepman, M. Knipper, H. Kremer, et al. Scaffold protein harmonin (USH1C) provides molecular links between Usher syndrome type 1 and type 2 Hum. Mol. Genet., December 15, 2005; 14(24): 3933 - 3943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D'Alterio, D. D.D. Tran, M. W.Y. A. Yeung, M. S.H. Hwang, M. A. Li, C. J. Arana, V. K. Mulligan, M. Kubesh, P. Sharma, M. Chase, et al. Drosophila melanogaster Cad99C, the orthologue of human Usher cadherin PCDH15, regulates the length of microvilli J. Cell Biol., November 7, 2005; 171(3): 549 - 558. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. El-Amraoui and C. Petit Usher I syndrome: unravelling the mechanisms that underlie the cohesion of the growing hair bundle in inner ear sensory cells J. Cell Sci., October 15, 2005; 118(20): 4593 - 4603. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Krendel and M. S. Mooseker Myosins: Tails (and Heads) of Functional Diversity Physiology, August 1, 2005; 20(4): 239 - 251. [Abstract] [Full Text] [PDF]
|
|