Mechanistic insights into kindlin function and regulation
Kindlins are FERM domain containing adapter proteins known for their role in integrin inside-out and outside-in activation and signalling. In addition, they mediate various integrin-independent processes. How kindlins perform diverse functions under different cellular contexts is not yet fully eluci...
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| Format: | Thesis-Doctor of Philosophy |
| Language: | English |
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Nanyang Technological University
2022
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| Online Access: | https://hdl.handle.net/10356/155651 |
| _version_ | 1826110248094531584 |
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| author | Levitskaya, Zarina |
| author2 | Tan Suet Mien |
| author_facet | Tan Suet Mien Levitskaya, Zarina |
| author_sort | Levitskaya, Zarina |
| collection | NTU |
| description | Kindlins are FERM domain containing adapter proteins known for their role in integrin inside-out and outside-in activation and signalling. In addition, they mediate various integrin-independent processes. How kindlins perform diverse functions under different cellular contexts is not yet fully elucidated. Here, regulatory mechanisms behind kindlin and integrin activity with respect to their post-translational modifications and interacting partners are explored. The first part of thesis addresses auto-inhibitory mechanism of kindlin-3 oligomerization. Kindlin-3 trimer formation was validated in vitro, and disruption of trimerization resulted in increased integrin-mediated cell spreading and adhesion. In the second part, newly identified interaction of kindlin-3 is explored, uncovering its role in translational regulation. Overall, findings on intra- and inter-molecular interactions of kindlins have opened up new areas for exploration of their functions and potential implications in disease progression. |
| first_indexed | 2024-10-01T02:31:17Z |
| format | Thesis-Doctor of Philosophy |
| id | ntu-10356/155651 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:31:17Z |
| publishDate | 2022 |
| publisher | Nanyang Technological University |
| record_format | dspace |
| spelling | ntu-10356/1556512023-02-28T18:31:38Z Mechanistic insights into kindlin function and regulation Levitskaya, Zarina Tan Suet Mien School of Biological Sciences SMTan@ntu.edu.sg Science::Biological sciences::Molecular biology Kindlins are FERM domain containing adapter proteins known for their role in integrin inside-out and outside-in activation and signalling. In addition, they mediate various integrin-independent processes. How kindlins perform diverse functions under different cellular contexts is not yet fully elucidated. Here, regulatory mechanisms behind kindlin and integrin activity with respect to their post-translational modifications and interacting partners are explored. The first part of thesis addresses auto-inhibitory mechanism of kindlin-3 oligomerization. Kindlin-3 trimer formation was validated in vitro, and disruption of trimerization resulted in increased integrin-mediated cell spreading and adhesion. In the second part, newly identified interaction of kindlin-3 is explored, uncovering its role in translational regulation. Overall, findings on intra- and inter-molecular interactions of kindlins have opened up new areas for exploration of their functions and potential implications in disease progression. Doctor of Philosophy 2022-03-10T04:26:20Z 2022-03-10T04:26:20Z 2022 Thesis-Doctor of Philosophy Levitskaya, Z. (2022). Mechanistic insights into kindlin function and regulation. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/155651 https://hdl.handle.net/10356/155651 10.32657/10356/155651 en This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). application/pdf Nanyang Technological University |
| spellingShingle | Science::Biological sciences::Molecular biology Levitskaya, Zarina Mechanistic insights into kindlin function and regulation |
| title | Mechanistic insights into kindlin function and regulation |
| title_full | Mechanistic insights into kindlin function and regulation |
| title_fullStr | Mechanistic insights into kindlin function and regulation |
| title_full_unstemmed | Mechanistic insights into kindlin function and regulation |
| title_short | Mechanistic insights into kindlin function and regulation |
| title_sort | mechanistic insights into kindlin function and regulation |
| topic | Science::Biological sciences::Molecular biology |
| url | https://hdl.handle.net/10356/155651 |
| work_keys_str_mv | AT levitskayazarina mechanisticinsightsintokindlinfunctionandregulation |