Details

Autor(en) / Beteiligte

• Tian, Guilian
• Zhou, Yun
• Hajkova, Dagmar
• Miyagi, Masaru
• Dinculescu, Astra
• Hauswirth, William W.
• Palczewski, Krzysztof
• Geng, Ruishuang
• Alagramam, Kumar N.
• Isosomppi, Juha
• Sankila, Eeva-Marja
• Flannery, John G.
• Imanishi, Yoshikazu

Titel

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

Ist Teil von

• The Journal of biological chemistry, 2009-07, Vol.284 (28), p.18980-18993

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2009

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.