title: Regulation of epithelial cell polarity by PAR-3 depends on Girdin transcription and Girdin-Gαi3 signaling.
abstract: Epithelial apicobasal polarity has fundamental roles in epithelial physiology and morphogenesis. The PAR complex, comprising PAR-3, PAR-6 and atypical protein kinase C (aPKC), is involved in determining cell polarity in various biological contexts, including in epithelial cells. However, it is not fully understood how the PAR complex induces apicobasal polarity. In this study, we found that PAR-3 regulates the protein expression of Girdin (also known as GIV or CCDC88A), a guanine-nucleotide-exchange factor (GEF) for heterotrimeric Gαi subunits, at the transcriptional level by cooperating with the AP-2 transcription factor. In addition, we confirmed that PAR-3 physically interacts with Girdin, and show that Girdin, together with the Gαi3 (also known as GNAI3), controls tight junction formation, apical domain development and actin organization downstream of PAR-3. Taken together, our findings suggest that transcriptional upregulation of Girdin expression and Girdin-Gαi3 signaling play crucial roles in regulating epithelial apicobasal polarity through the PAR complex.
authors.affiliation: Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Kakuwa
authors.affiliation: Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan Department of Molecular Medical Science, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Akimoto
authors.affiliation: Department of Human Genome Research, Kazusa DNA Research Institute, 2-6-7 Kazusa-Kamatari, Kisarazu, Chiba 292-0818, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Koga
authors.affiliation: Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan ohnos@med.yokohama-cu.ac.jp.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohno
mesh_terms: D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D002450:Cell Communication; D016764:Cell Polarity; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D008840:Microfilament Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D019108:Tight Junctions / Q000378:metabolism; D050656:Transcription Factor AP-2 / Q000378:metabolism; D014158:Transcription, Genetic; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: C502451:CCDC88A protein, human; D002352:Carrier Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; C472451:Pard3 protein, rat; D012333:RNA, Messenger; D050656:Transcription Factor AP-2; D033921:Vesicular Transport Proteins; C115015:PKC-3 protein; D011493:Protein Kinase C; C498819:GNAI3 protein, human; D019206:GTP-Binding Protein alpha Subunits, Gi-Go
keywords: AP-2; Apicobasal polarity; Girdin; Gαi3; PAR–aPKC complex; Transcription