A Cell Junctional Protein Network Associated with Connexin-26

International Journal of Molecular Sciences

AnaC. Batissoco¹  Rodrigo Salazar-Silva¹  ReginaC. Mingroni-Netto¹  LucianaA. Haddad¹  Jeanne Oiticica²  RicardoF. Bento² 

[1] Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Instituto de Biociências, Universidade de São Paulo, 05508-090 São Paulo, Brazil;Laboratório de Otorrinolaringologia/LIM32, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, 01246-903 São Paulo, Brazil;

关键词: connexin;    connexin 26;    GJB2 gene;    deafness;    protein-protein interaction;    TJP1;    CGN;    FLNB;    DAAM1;    organ of Corti;   

DOI  :  10.3390/ijms19092535

来源: DOAJ

【 摘 要 】

GJB2 mutations are the leading cause of non-syndromic inherited hearing loss. GJB2 encodes connexin-26 (CX26), which is a connexin (CX) family protein expressed in cochlea, skin, liver, and brain, displaying short cytoplasmic N-termini and C-termini. We searched for CX26 C-terminus binding partners by affinity capture and identified 12 unique proteins associated with cell junctions or cytoskeleton (CGN, DAAM1, FLNB, GAPDH, HOMER2, MAP7, MAPRE2 (EB2), JUP, PTK2B, RAI14, TJP1, and VCL) by using mass spectrometry. We show that, similar to other CX family members, CX26 co-fractionates with TJP1, VCL, and EB2 (EB1 paralogue) as well as the membrane-associated protein ASS1. The adaptor protein CGN (cingulin) co-immuno-precipitates with CX26, ASS1, and TJP1. In addition, CGN co-immunoprecipitation with CX30, CX31, and CX43 indicates that CX association is independent on the CX C-terminus length or sequence. CX26, CGN, FLNB, and DAMM1 were shown to distribute to the organ of Corti and hepatocyte plasma membrane. In the mouse liver, CX26 and TJP1 co-localized at the plasma membrane. In conclusion, CX26 associates with components of other membrane junctions that integrate with the cytoskeleton.

【 授权许可】

Unknown