NDLI: Clarin-1, Encoded by the Usher Syndrome III Causative Gene, Forms a Membranous Microdomain

Content Provider	PubMed Central
Author	Tian, Guilian Zhou, Yun Hajkova, Dagmar Miyagi, Masaru Dinculescu, Astra Hauswirth, William W. Palczewski, Krzysztof Geng, Ruishuang Alagramam, Kumar N. Juha, Isosomppi Sankila, Eeva-marja Flannery, John G. Imanishi, Yoshikazu
Abstract	Clarin-1 is the protein product encoded by the gene mutated in Usher syndrome III. Although the molecular function of clarin-1 is unknown, its primary structure predicts four transmembrane domains similar to a large family of membrane proteins that include tetraspanins. Here we investigated the role of clarin-1 by using heterologous expression and in vivo model systems. When expressed in HEK293 cells, clarin-1 localized to the plasma membrane and concentrated in low density compartments distinct from lipid rafts. Clarin-1 reorganized actin filament structures and induced lamellipodia. This actin-reorganizing function was absent in the modified protein encoded by the most prevalent North American Usher syndrome III mutation, the N48K form of clarin-1 deficient in N-linked glycosylation. Proteomics analyses revealed a number of clarin-1-interacting proteins involved in cell-cell adhesion, focal adhesions, cell migration, tight junctions, and regulation of the actin cytoskeleton. Consistent with the hypothesized role of clarin-1 in actin organization, F-actin-enriched stereocilia of auditory hair cells evidenced structural disorganization in Clrn1 −/− mice. These observations suggest a possible role for clarin-1 in the regulation and homeostasis of actin filaments, and link clarin-1 to the interactive network of Usher syndrome gene products.
Related Links	http://dx.doi.org/10.1074/jbc.m109.003160
Ending Page	18993
Page Count	14
Starting Page	18980
File Format	PDF
ISSN	00219258
e-ISSN	1083351X
Journal	The Journal of Biological Chemistry
Issue Number	28
Volume Number	284
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2009-07-10
Access Restriction	Open
Rights Holder	American Society for Biochemistry and Molecular Biology
Subject Keyword	Cell Biology Biochemistry Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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Clarin-1, Encoded by the Usher Syndrome III Causative Gene, Forms a Membranous Microdomain POSSIBLE ROLE OF CLARIN-1 IN ORGANIZING THE ACTIN CYTOSKELETON

Clarin-1, Encoded by the Usher Syndrome III Causative Gene, Forms a Membranous Microdomain: POSSIBLE ROLE OF CLARIN-1 IN ORGANIZING THE ACTIN CYTOSKELETON

The Mechanosensory Structure of the Hair Cell Requires Clarin-1, a Protein Encoded by Usher Syndrome III Causative Gene

Cone Structure in Patients With Usher Syndrome Type III and Mutations in the Clarin 1 Gene

Usher syndrome IIIA gene clarin-1 is essential for hair cell function and associated neural activation†

Usher syndrome IIIA gene clarin-1 is essential for hair cell function and associated neural activation†

Cone Structure in Patients With Usher Syndrome Type III and Mutations in the Clarin 1 Gene

Domain analyses of Usher syndrome causing Clarin-1 and GPR98 protein models

Zebrafish Models for the Mechanosensory Hair Cell Dysfunction in Usher Syndrome 3 Reveal That Clarin-1 Is an Essential Hair Bundle Protein

Clarin-1, Encoded by the Usher Syndrome III Causative Gene, Forms a Membranous Microdomain

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Domain analyses of Usher syndrome causing Clarin-1 and GPR98 protein models

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Clarin-1, Encoded by the Usher Syndrome III Causative Gene, Forms a Membranous Microdomain