KANK1 shapes focal adhesions by orchestrating protein binding, mechanical force sensing, and phase separation
Summary: Focal adhesions (FAs) are dynamic protein assemblies that connect cytoskeletons to the extracellular matrix and are crucial for cell adhesion and migration. KANKs are scaffold proteins that encircle FAs and act as key regulators of FA dynamics, but the molecular mechanism underlying their s...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-11-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723013335 |
| _version_ | 1797448112347807744 |
|---|---|
| author | Kaitong Guo Jing Zhang Pei Huang Yuqun Xu Wenfei Pan Kaiyue Li Lu Chen Li Luo Weichun Yu Shuai Chen Sicong He Zhiyi Wei Cong Yu |
| author_facet | Kaitong Guo Jing Zhang Pei Huang Yuqun Xu Wenfei Pan Kaiyue Li Lu Chen Li Luo Weichun Yu Shuai Chen Sicong He Zhiyi Wei Cong Yu |
| author_sort | Kaitong Guo |
| collection | DOAJ |
| description | Summary: Focal adhesions (FAs) are dynamic protein assemblies that connect cytoskeletons to the extracellular matrix and are crucial for cell adhesion and migration. KANKs are scaffold proteins that encircle FAs and act as key regulators of FA dynamics, but the molecular mechanism underlying their specified localization and functions remains poorly understood. Here, we determine the KANK1 structures in complex with talin and liprin-β, respectively. These structures, combined with our biochemical and cellular analyses, demonstrate how KANK1 scaffolds the FA core and associated proteins to modulate the FA shape in response to mechanical force. Additionally, we find that KANK1 undergoes liquid-liquid phase separation (LLPS), which is important for its localization at the FA edge and cytoskeleton connections to FAs. Our findings not only indicate the molecular basis of KANKs in bridging the core and periphery of FAs but also provide insights into the LLPS-mediated dynamic regulation of FA morphology. |
| first_indexed | 2024-03-09T14:05:44Z |
| format | Article |
| id | doaj.art-4b50d3a564c545ec9bf7cfd42e5ceead |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-09T14:05:44Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-4b50d3a564c545ec9bf7cfd42e5ceead2023-11-30T05:06:45ZengElsevierCell Reports2211-12472023-11-014211113321KANK1 shapes focal adhesions by orchestrating protein binding, mechanical force sensing, and phase separationKaitong Guo0Jing Zhang1Pei Huang2Yuqun Xu3Wenfei Pan4Kaiyue Li5Lu Chen6Li Luo7Weichun Yu8Shuai Chen9Sicong He10Zhiyi Wei11Cong Yu12School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China; Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, and Shenzhen Key Laboratory of Cell Microenvironment, Shenzhen 518055, Guangdong, ChinaSchool of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China; Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, and Shenzhen Key Laboratory of Cell Microenvironment, Shenzhen 518055, Guangdong, China; Brain Research Center, Southern University of Science and Technology, Shenzhen, Guangdong 518055, ChinaSchool of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China; Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, and Shenzhen Key Laboratory of Cell Microenvironment, Shenzhen 518055, Guangdong, ChinaSchool of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China; Brain Research Center, Southern University of Science and Technology, Shenzhen, Guangdong 518055, ChinaSchool of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong 518055, ChinaSchool of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong 518055, ChinaSchool of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China; Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, and Shenzhen Key Laboratory of Cell Microenvironment, Shenzhen 518055, Guangdong, ChinaSchool of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong 518055, ChinaSchool of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China; Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, and Shenzhen Key Laboratory of Cell Microenvironment, Shenzhen 518055, Guangdong, ChinaSchool of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China; Brain Research Center, Southern University of Science and Technology, Shenzhen, Guangdong 518055, ChinaSchool of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong 518055, ChinaSchool of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China; Brain Research Center, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China; Corresponding authorSchool of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China; Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, and Shenzhen Key Laboratory of Cell Microenvironment, Shenzhen 518055, Guangdong, China; Corresponding authorSummary: Focal adhesions (FAs) are dynamic protein assemblies that connect cytoskeletons to the extracellular matrix and are crucial for cell adhesion and migration. KANKs are scaffold proteins that encircle FAs and act as key regulators of FA dynamics, but the molecular mechanism underlying their specified localization and functions remains poorly understood. Here, we determine the KANK1 structures in complex with talin and liprin-β, respectively. These structures, combined with our biochemical and cellular analyses, demonstrate how KANK1 scaffolds the FA core and associated proteins to modulate the FA shape in response to mechanical force. Additionally, we find that KANK1 undergoes liquid-liquid phase separation (LLPS), which is important for its localization at the FA edge and cytoskeleton connections to FAs. Our findings not only indicate the molecular basis of KANKs in bridging the core and periphery of FAs but also provide insights into the LLPS-mediated dynamic regulation of FA morphology.http://www.sciencedirect.com/science/article/pii/S2211124723013335CP: Molecular biology |
| spellingShingle | Kaitong Guo Jing Zhang Pei Huang Yuqun Xu Wenfei Pan Kaiyue Li Lu Chen Li Luo Weichun Yu Shuai Chen Sicong He Zhiyi Wei Cong Yu KANK1 shapes focal adhesions by orchestrating protein binding, mechanical force sensing, and phase separation Cell Reports CP: Molecular biology |
| title | KANK1 shapes focal adhesions by orchestrating protein binding, mechanical force sensing, and phase separation |
| title_full | KANK1 shapes focal adhesions by orchestrating protein binding, mechanical force sensing, and phase separation |
| title_fullStr | KANK1 shapes focal adhesions by orchestrating protein binding, mechanical force sensing, and phase separation |
| title_full_unstemmed | KANK1 shapes focal adhesions by orchestrating protein binding, mechanical force sensing, and phase separation |
| title_short | KANK1 shapes focal adhesions by orchestrating protein binding, mechanical force sensing, and phase separation |
| title_sort | kank1 shapes focal adhesions by orchestrating protein binding mechanical force sensing and phase separation |
| topic | CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723013335 |
| work_keys_str_mv | AT kaitongguo kank1shapesfocaladhesionsbyorchestratingproteinbindingmechanicalforcesensingandphaseseparation AT jingzhang kank1shapesfocaladhesionsbyorchestratingproteinbindingmechanicalforcesensingandphaseseparation AT peihuang kank1shapesfocaladhesionsbyorchestratingproteinbindingmechanicalforcesensingandphaseseparation AT yuqunxu kank1shapesfocaladhesionsbyorchestratingproteinbindingmechanicalforcesensingandphaseseparation AT wenfeipan kank1shapesfocaladhesionsbyorchestratingproteinbindingmechanicalforcesensingandphaseseparation AT kaiyueli kank1shapesfocaladhesionsbyorchestratingproteinbindingmechanicalforcesensingandphaseseparation AT luchen kank1shapesfocaladhesionsbyorchestratingproteinbindingmechanicalforcesensingandphaseseparation AT liluo kank1shapesfocaladhesionsbyorchestratingproteinbindingmechanicalforcesensingandphaseseparation AT weichunyu kank1shapesfocaladhesionsbyorchestratingproteinbindingmechanicalforcesensingandphaseseparation AT shuaichen kank1shapesfocaladhesionsbyorchestratingproteinbindingmechanicalforcesensingandphaseseparation AT siconghe kank1shapesfocaladhesionsbyorchestratingproteinbindingmechanicalforcesensingandphaseseparation AT zhiyiwei kank1shapesfocaladhesionsbyorchestratingproteinbindingmechanicalforcesensingandphaseseparation AT congyu kank1shapesfocaladhesionsbyorchestratingproteinbindingmechanicalforcesensingandphaseseparation |