TIMAP, a Regulatory Subunit of Protein Phosphatase 1, Inhibits In Vitro Neuronal Differentiation
TIMAP (TGF-β-inhibited membrane associated protein) is abundant in endothelial cells, and it has been regarded as a member of the myosin phosphatase targeting protein (MYPT) family. Our workgroup previously identified several interacting protein partners of TIMAP and proved its regulatory subunit ro...
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| Format: | Article |
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/24/17360 |
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| author | Márton Fonódi Zsófia Thalwieser Csilla Csortos Anita Boratkó |
| author_facet | Márton Fonódi Zsófia Thalwieser Csilla Csortos Anita Boratkó |
| author_sort | Márton Fonódi |
| collection | DOAJ |
| description | TIMAP (TGF-β-inhibited membrane associated protein) is abundant in endothelial cells, and it has been regarded as a member of the myosin phosphatase targeting protein (MYPT) family. Our workgroup previously identified several interacting protein partners of TIMAP and proved its regulatory subunit role for protein phosphatase 1 catalytic subunit (PP1c). TIMAP is also expressed in neuronal cells, but details of its function have not been studied yet. Therefore, we aimed to explore the role of TIMAP in neuronal cells, especially during differentiation. Expression of TIMAP was proved both at mRNA and protein levels in SH-SY5Y human neuroblastoma cells. Differentiation of SH-SY5Y cells was optimized and proved by the detection of neuronal differentiation markers, such as β3-tubulin, nestin and inhibitor of differentiation 1 (ID1) using qPCR and Western blot. We found downregulation of TIMAP during differentiation. In accordance with this, overexpression of recombinant TIMAP attenuated the differentiation of neuronal cells. Moreover, the subcellular localization of TIMAP has changed during differentiation as it translocated from the plasma membrane into the nucleus. The nuclear interactome of TIMAP revealed more than 50 proteins, offering the possibility to further investigate the role of TIMAP in several key physiological pathways of neuronal cells. |
| first_indexed | 2024-03-08T20:41:53Z |
| format | Article |
| id | doaj.art-76f77d66c0b949e9be1077287534dd81 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T20:41:53Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-76f77d66c0b949e9be1077287534dd812023-12-22T14:14:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0124241736010.3390/ijms242417360TIMAP, a Regulatory Subunit of Protein Phosphatase 1, Inhibits In Vitro Neuronal DifferentiationMárton Fonódi0Zsófia Thalwieser1Csilla Csortos2Anita Boratkó3Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem Tér 1, H-4032 Debrecen, HungaryDepartment of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem Tér 1, H-4032 Debrecen, HungaryDepartment of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem Tér 1, H-4032 Debrecen, HungaryDepartment of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem Tér 1, H-4032 Debrecen, HungaryTIMAP (TGF-β-inhibited membrane associated protein) is abundant in endothelial cells, and it has been regarded as a member of the myosin phosphatase targeting protein (MYPT) family. Our workgroup previously identified several interacting protein partners of TIMAP and proved its regulatory subunit role for protein phosphatase 1 catalytic subunit (PP1c). TIMAP is also expressed in neuronal cells, but details of its function have not been studied yet. Therefore, we aimed to explore the role of TIMAP in neuronal cells, especially during differentiation. Expression of TIMAP was proved both at mRNA and protein levels in SH-SY5Y human neuroblastoma cells. Differentiation of SH-SY5Y cells was optimized and proved by the detection of neuronal differentiation markers, such as β3-tubulin, nestin and inhibitor of differentiation 1 (ID1) using qPCR and Western blot. We found downregulation of TIMAP during differentiation. In accordance with this, overexpression of recombinant TIMAP attenuated the differentiation of neuronal cells. Moreover, the subcellular localization of TIMAP has changed during differentiation as it translocated from the plasma membrane into the nucleus. The nuclear interactome of TIMAP revealed more than 50 proteins, offering the possibility to further investigate the role of TIMAP in several key physiological pathways of neuronal cells.https://www.mdpi.com/1422-0067/24/24/17360TIMAPprotein phosphataseneuroblastomadifferentiationinteractome |
| spellingShingle | Márton Fonódi Zsófia Thalwieser Csilla Csortos Anita Boratkó TIMAP, a Regulatory Subunit of Protein Phosphatase 1, Inhibits In Vitro Neuronal Differentiation International Journal of Molecular Sciences TIMAP protein phosphatase neuroblastoma differentiation interactome |
| title | TIMAP, a Regulatory Subunit of Protein Phosphatase 1, Inhibits In Vitro Neuronal Differentiation |
| title_full | TIMAP, a Regulatory Subunit of Protein Phosphatase 1, Inhibits In Vitro Neuronal Differentiation |
| title_fullStr | TIMAP, a Regulatory Subunit of Protein Phosphatase 1, Inhibits In Vitro Neuronal Differentiation |
| title_full_unstemmed | TIMAP, a Regulatory Subunit of Protein Phosphatase 1, Inhibits In Vitro Neuronal Differentiation |
| title_short | TIMAP, a Regulatory Subunit of Protein Phosphatase 1, Inhibits In Vitro Neuronal Differentiation |
| title_sort | timap a regulatory subunit of protein phosphatase 1 inhibits in vitro neuronal differentiation |
| topic | TIMAP protein phosphatase neuroblastoma differentiation interactome |
| url | https://www.mdpi.com/1422-0067/24/24/17360 |
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