Reference - Detail
| RRC ID | 28602 |
|---|---|
| Author | Hirate Y, Hirahara S, Inoue K, Suzuki A, Alarcon VB, Akimoto K, Hirai T, Hara T, Adachi M, Chida K, Ohno S, Marikawa Y, Nakao K, Shimono A, Sasaki H. |
| Title | Polarity-dependent distribution of angiomotin localizes Hippo signaling in preimplantation embryos. |
| Journal | Curr Biol |
| Abstract |
BACKGROUND:In preimplantation mouse embryos, the first cell fate specification to the trophectoderm or inner cell mass occurs by the early blastocyst stage. The cell fate is controlled by cell position-dependent Hippo signaling, although the mechanisms underlying position-dependent Hippo signaling are unknown. RESULTS:We show that a combination of cell polarity and cell-cell adhesion establishes position-dependent Hippo signaling, where the outer and inner cells are polar and nonpolar, respectively. The junction-associated proteins angiomotin (Amot) and angiomotin-like 2 (Amotl2) are essential for Hippo pathway activation and appropriate cell fate specification. In the nonpolar inner cells, Amot localizes to adherens junctions (AJs), and cell-cell adhesion activates the Hippo pathway. In the outer cells, the cell polarity sequesters Amot from basolateral AJs to apical domains, thereby suppressing Hippo signaling. The N-terminal domain of Amot is required for actin binding, Nf2/Merlin-mediated association with the E-cadherin complex, and interaction with Lats protein kinase. In AJs, S176 in the N-terminal domain of Amot is phosphorylated by Lats, which inhibits the actin-binding activity, thereby stabilizing the Amot-Lats interaction to activate the Hippo pathway. CONCLUSIONS:We propose that the phosphorylation of S176 in Amot is a critical step for activation of the Hippo pathway in AJs and that cell polarity disconnects the Hippo pathway from cell-cell adhesion by sequestering Amot from AJs. This mechanism converts positional information into differential Hippo signaling, thereby leading to differential cell fates. |
| Volume | 23(13) |
| Pages | 1181-94 |
| Published | 2013-7-8 |
| DOI | 10.1016/j.cub.2013.05.014 |
| PII | S0960-9822(13)00577-0 |
| PMID | 23791731 |
| PMC | PMC3742369 |
| MeSH | Adherens Junctions / metabolism Angiomotins Animals Blastocyst / metabolism* Cell Adhesion Cell Polarity* Gene Expression Regulation, Developmental* Hippo Signaling Pathway Intercellular Signaling Peptides and Proteins / genetics* Intercellular Signaling Peptides and Proteins / metabolism Mice Microfilament Proteins / genetics* Microfilament Proteins / metabolism Phosphorylation Polymerase Chain Reaction Protein Serine-Threonine Kinases / genetics* Protein Serine-Threonine Kinases / metabolism Signal Transduction* Tumor Suppressor Proteins / metabolism |
| IF | 9.601 |
| Times Cited | 190 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| Resource | |
| DNA material | pcDNA3.1-pA83-aPKC lambda KD (RDB012202) HA-Amot130/pcDNA3.1-pA83 (RDB012203) HA-Amot80/pcDNA3.1-pA83 (RDB012204) HA-Amot130-delta CC/pcDNA3.1-pA83 (RDB012205) HA-Amot130-m5/pcDNA3.1-pA83 (RDB012206) HA-Amot130-delta PDZbd/pcDNA3.1-pA83 (RDB012207) HA-Amot130-S176A/pcDNA3.1-pA83 (RDB012208) HA-Amot130-S176E/pcDNA3.1-pA83 (RDB012209) HA-Merlin/pCAG-pA83 (RDB012210) HA-Amot-delta(45-100)/pcDNA3.1-pA83 (RDB012211) HA-Amot-delta(101-141)/pcDNA3.1-pA83 (RDB012212) pCMV/SV-Flag-Lats2 (RDB012213) pCMV/SV-Flag-Lats2-KD (RDB012214) Ecad-Flag/pCAG (RDB012215) E-Cadherin-delta C-Flag/pCAG (RDB012216) |