| Project/Area Number |
15K08138
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
General anatomy (including histology/embryology)
|
|---|
| Research Institution | Yokohama City University |
|---|
Principal Investigator |
Nakaya Masa-aki 横浜市立大学, 医学研究科, 特任助教 (70422095)
|
|---|
| Research Collaborator |
Moriyama Kayano
|
|---|
| Project Period (FY) |
2015-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | 細胞極性 / 平面極性 / タンパク質リン酸化 / プロテオミクス / 形態形成 / プロテオミクス解析 / Wnt-PCPシグナル / aPKC-PARシグナル / aPKC / Daam1 / ３次元培養法 |
|---|
| Outline of Final Research Achievements |
Proper regulation of cell polarity which we can recognize as obviously cellular asymmetries of cellular components, such as planar cell polarity in x-y plane (PCP) and apico-basal polarity (z axis), is essential to form correct three-dimensional architecture of the body. However, whether and how apico-basal polarity and PCP mutually interact remains unclear. In this study, we show that atypical protein kinase C (aPKC), a key regulator for apical-basal polarity, genetically interact in mice with Daam1 (Dshevelled associated activator of morphogenesis 1), a member of the Wnt-PCP signaling. Functional experiments in Xenopus embryo further revealed that aPKC complement loss of Daam1 phenotype. Biochemically, aPKC and Daam1 physically interact through Lgl-1. Consistently, loss of Lgl in Xenopus phenocopies loss of function of aPKC or Daam1. These results reveal a connection between the two key polarity signaling, PCP and apicobasal polarity; aPKC contributes to PCP through Lgl.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究では、「細胞極性病」という新たな疾患概念を確立に注力した。細胞極性異常は上皮由来の癌の病理学的特徴から推測された原因の1つであるが、近年の分子生物学的研究成果から、細胞極性を制御する一連の遺伝子群が先天性奇形など、他の疾患群の原因となる事が明らかとなってきている。本研究では、この点に着目して基礎医学的手法を駆使した研究を遂行し、バイオ・インフォマティクス・データベースに蓄積されている膨大な情報と照らし合わせて、細胞極性病を定義する病態の探索と検証を行った。
|
