The cell adhesion molecule TMIGD1 binds to moesin and regulates tubulin acetylation and cell migration
Abstract Background The cell adhesion molecule transmembrane and immunoglobulin (Ig) domain containing1 (TMIGD1) is a novel tumor suppressor that plays important roles in regulating cell–cell adhesion, cell proliferation and cell cycle. However, the mechanisms of TMIGD1 signaling are not yet fully e...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-09-01
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| Series: | Journal of Biomedical Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12929-021-00757-z |
| _version_ | 1819139936344866816 |
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| author | Nader Rahimi Rachel X. Y. Ho Kevin Brown Chandler Kyle Oliver Corcino De La Cena Razie Amraei Ashley J. Mitchel Nels Engblom Catherine E. Costello |
| author_facet | Nader Rahimi Rachel X. Y. Ho Kevin Brown Chandler Kyle Oliver Corcino De La Cena Razie Amraei Ashley J. Mitchel Nels Engblom Catherine E. Costello |
| author_sort | Nader Rahimi |
| collection | DOAJ |
| description | Abstract Background The cell adhesion molecule transmembrane and immunoglobulin (Ig) domain containing1 (TMIGD1) is a novel tumor suppressor that plays important roles in regulating cell–cell adhesion, cell proliferation and cell cycle. However, the mechanisms of TMIGD1 signaling are not yet fully elucidated. Results TMIGD1 binds to the ERM family proteins moesin and ezrin, and an evolutionarily conserved RRKK motif on the carboxyl terminus of TMIGD1 mediates the interaction of TMIGD1 with the N-terminal ERM domains of moesin and ezrin. TMIGD1 governs the apical localization of moesin and ezrin, as the loss of TMIGD1 in mice altered apical localization of moesin and ezrin in epithelial cells. In cell culture, TMIGD1 inhibited moesin-induced filopodia-like protrusions and cell migration. More importantly, TMIGD1 stimulated the Lysine (K40) acetylation of α-tubulin and promoted mitotic spindle organization and CRISPR/Cas9-mediated knockout of moesin impaired the TMIGD1-mediated acetylation of α-tubulin and filamentous (F)-actin organization. Conclusions TMIGD1 binds to moesin and ezrin, and regulates their cellular localization. Moesin plays critical roles in TMIGD1-dependent acetylation of α-tubulin, mitotic spindle organization and cell migration. Our findings offer a molecular framework for understanding the complex functional interplay between TMIGD1 and the ERM family proteins in the regulation of cell adhesion and mitotic spindle assembly, and have wide-ranging implications in physiological and pathological processes such as cancer progression. |
| first_indexed | 2024-12-22T11:30:35Z |
| format | Article |
| id | doaj.art-905793abb0ac47a897621979f2d29b63 |
| institution | Directory Open Access Journal |
| issn | 1423-0127 |
| language | English |
| last_indexed | 2024-12-22T11:30:35Z |
| publishDate | 2021-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biomedical Science |
| spelling | doaj.art-905793abb0ac47a897621979f2d29b632022-12-21T18:27:37ZengBMCJournal of Biomedical Science1423-01272021-09-0128111210.1186/s12929-021-00757-zThe cell adhesion molecule TMIGD1 binds to moesin and regulates tubulin acetylation and cell migrationNader Rahimi0Rachel X. Y. Ho1Kevin Brown Chandler2Kyle Oliver Corcino De La Cena3Razie Amraei4Ashley J. Mitchel5Nels Engblom6Catherine E. Costello7Department of Pathology, School of Medicine, Boston University Medical CampusDepartment of Pathology, School of Medicine, Boston University Medical CampusCenter for Biomedical Mass Spectrometry, Boston University School of MedicineDepartment of Pathology, School of Medicine, Boston University Medical CampusDepartment of Pathology, School of Medicine, Boston University Medical CampusDepartment of Pathology, School of Medicine, Boston University Medical CampusDepartment of Pathology, School of Medicine, Boston University Medical CampusCenter for Biomedical Mass Spectrometry, Boston University School of MedicineAbstract Background The cell adhesion molecule transmembrane and immunoglobulin (Ig) domain containing1 (TMIGD1) is a novel tumor suppressor that plays important roles in regulating cell–cell adhesion, cell proliferation and cell cycle. However, the mechanisms of TMIGD1 signaling are not yet fully elucidated. Results TMIGD1 binds to the ERM family proteins moesin and ezrin, and an evolutionarily conserved RRKK motif on the carboxyl terminus of TMIGD1 mediates the interaction of TMIGD1 with the N-terminal ERM domains of moesin and ezrin. TMIGD1 governs the apical localization of moesin and ezrin, as the loss of TMIGD1 in mice altered apical localization of moesin and ezrin in epithelial cells. In cell culture, TMIGD1 inhibited moesin-induced filopodia-like protrusions and cell migration. More importantly, TMIGD1 stimulated the Lysine (K40) acetylation of α-tubulin and promoted mitotic spindle organization and CRISPR/Cas9-mediated knockout of moesin impaired the TMIGD1-mediated acetylation of α-tubulin and filamentous (F)-actin organization. Conclusions TMIGD1 binds to moesin and ezrin, and regulates their cellular localization. Moesin plays critical roles in TMIGD1-dependent acetylation of α-tubulin, mitotic spindle organization and cell migration. Our findings offer a molecular framework for understanding the complex functional interplay between TMIGD1 and the ERM family proteins in the regulation of cell adhesion and mitotic spindle assembly, and have wide-ranging implications in physiological and pathological processes such as cancer progression.https://doi.org/10.1186/s12929-021-00757-zTMIGD1MoesinEzrinERM family proteinsTubulin acetylationMitotic spindle |
| spellingShingle | Nader Rahimi Rachel X. Y. Ho Kevin Brown Chandler Kyle Oliver Corcino De La Cena Razie Amraei Ashley J. Mitchel Nels Engblom Catherine E. Costello The cell adhesion molecule TMIGD1 binds to moesin and regulates tubulin acetylation and cell migration Journal of Biomedical Science TMIGD1 Moesin Ezrin ERM family proteins Tubulin acetylation Mitotic spindle |
| title | The cell adhesion molecule TMIGD1 binds to moesin and regulates tubulin acetylation and cell migration |
| title_full | The cell adhesion molecule TMIGD1 binds to moesin and regulates tubulin acetylation and cell migration |
| title_fullStr | The cell adhesion molecule TMIGD1 binds to moesin and regulates tubulin acetylation and cell migration |
| title_full_unstemmed | The cell adhesion molecule TMIGD1 binds to moesin and regulates tubulin acetylation and cell migration |
| title_short | The cell adhesion molecule TMIGD1 binds to moesin and regulates tubulin acetylation and cell migration |
| title_sort | cell adhesion molecule tmigd1 binds to moesin and regulates tubulin acetylation and cell migration |
| topic | TMIGD1 Moesin Ezrin ERM family proteins Tubulin acetylation Mitotic spindle |
| url | https://doi.org/10.1186/s12929-021-00757-z |
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