Le 2. Overview of rare polymorphism (Table 2)Exon /Intron Exon5 Nucleotide Adjust c.G346A Minor Allele Frequency Amino Acid Domain Table 2. Overview with the 3 variants in KRGDB SGI TMPRSS3. Alter UCSC 1000G p.V116M SRCR 0.0015 0 0 0 Amino Acid Changep.V116M p.V291L p.V291LPhenotype Profound Likely Phenotype pathogenicReferences [10,11] This Study
International Journal ofMolecular SciencesCommunicationA Cell Junctional Protein Network Connected with ConnexinAna C. Batissoco 1,2, ID , Calpain inhibitor II supplier rodrigo SalazarSilva 1 , Jeanne Oiticica 2 , Ricardo F. Bento 2 Regina C. MingroniNetto 1 and Luciana A. HaddadID,Human Genome and Stem Cell Analysis Center, Department of Genetics and Evolutionary Biology, Instituto de Bioci cias, Universidade de S Paulo, 05508090 S Paulo, Brazil; [email protected] (R.S.S.); [email protected] (R.C.M.N.); [email protected] (L.A.H.) Laborat io de Otorrinolaringologia/LIM32, Hospital das Cl icas, Faculdade de Medicina, Universidade de S Paulo, 01246903 S Paulo, Brazil; [email protected] (J.O.); [email protected] (R.F.B.) Correspondence: [email protected]; Tel.: 5511Received: 17 July 2018; Accepted: 21 August 2018; Published: 27 AugustAbstract: GJB2 mutations are the leading cause of nonsyndromic inherited hearing loss. GJB2 encodes connexin26 (CX26), that is a connexin (CX) household protein expressed in cochlea, skin, liver, and brain, displaying short cytoplasmic Ntermini and Ctermini. We searched for CX26 Cterminus binding partners by affinity capture and identified 12 exclusive proteins linked with cell junctions or cytoskeleton (CGN, DAAM1, FLNB, GAPDH, HOMER2, MAP7, MAPRE2 (EB2), JUP, PTK2B, RAI14, TJP1, and VCL) by utilizing mass spectrometry. We show that, related to other CX family members, CX26 cofractionates with TJP1, VCL, and EB2 (EB1 paralogue) too as the membraneassociated protein ASS1. The adaptor protein CGN (cingulin) coimmunoprecipitates with CX26, ASS1, and TJP1. Additionally, CGN coimmunoprecipitation with CX30, CX31, and CX43 indicates that CX association is independent on the CX Cterminus length or sequence. CX26, CGN, FLNB, and DAMM1 had been shown to distribute towards the organ of Corti and hepatocyte plasma membrane. Inside the mouse liver, CX26 and TJP1 colocalized in the plasma membrane. In conclusion, CX26 associates with elements of other membrane junctions that integrate together with the cytoskeleton. Keyword phrases: connexin; connexin 26; GJB2 gene; deafness; proteinprotein interaction; TJP1; CGN; FLNB; DAAM1; organ of Corti1. Introduction The GJB2 gene encodes connexin 26 (CX26), which is a protein that plays central roles in hearing, promoting cochlear development, and sustaining auditory function inside the mature cochlea [1]. As well as the cochlea, expression of CX26 is also observed within the skin, the liver, the brain, the mammary gland, the salivary gland, the uterus, testis, the pancreas, lungs, the stomach, the thyroid, and the parathyroid [5]. GJB2 mutations will be the most frequent reason for nonsyndromic recessive hearing loss across diverse populations [6]. Moreover, some heterozygous GJB2 mutations behave within a dominant fashion, which leads to nonsyndromic autosomal dominant hearing loss or to the keratitisichthyosisdeafness syndrome [10]. In vertebrates, connexins (CX) assemble intercellular gap junctions (GJ), which outcome in the interaction among two distinct hemichannels from adjacent cells with each and every composed of six CX units. GJ straight enables the passage of numerous sma.
