What’s in a Gene? The Outstanding Diversity of <i>MAPT</i>
Tau protein is a microtubule-associated protein encoded by the <i>MAPT</i> gene that carries out a myriad of physiological functions and has been linked to certain pathologies collectively termed tauopathies, including Alzheimer’s disease, frontotemporal dementia, Huntington’s disease, p...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/5/840 |
| _version_ | 1797475405370753024 |
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| author | Daniel Ruiz-Gabarre Almudena Carnero-Espejo Jesús Ávila Vega García-Escudero |
| author_facet | Daniel Ruiz-Gabarre Almudena Carnero-Espejo Jesús Ávila Vega García-Escudero |
| author_sort | Daniel Ruiz-Gabarre |
| collection | DOAJ |
| description | Tau protein is a microtubule-associated protein encoded by the <i>MAPT</i> gene that carries out a myriad of physiological functions and has been linked to certain pathologies collectively termed tauopathies, including Alzheimer’s disease, frontotemporal dementia, Huntington’s disease, progressive supranuclear palsy, etc. Alternative splicing is a physiological process by which cells generate several transcripts from one single gene and may in turn give rise to different proteins from the same gene. <i>MAPT</i> transcripts have been proven to be subjected to alternative splicing, generating six main isoforms in the central nervous system. Research throughout the years has demonstrated that the splicing landscape of the <i>MAPT</i> gene is far more complex than that, including at least exon skipping events, the use of 3′ and 5′ alternative splice sites and, as has been recently discovered, also intron retention. In addition, <i>MAPT</i> alternative splicing has been showed to be regulated spatially and developmentally, further evidencing the complexity of the gene’s splicing regulation. It is unclear what would drive the need for the existence of so many isoforms encoded by the same gene, but a wide range of functions have been ascribed to these Tau isoforms, both in physiology and pathology. In this review we offer a comprehensive up-to-date exploration of the mechanisms leading to the outstanding diversity of isoforms expressed from the <i>MAPT</i> gene and the functions in which such isoforms are involved, including their potential role in the onset and development of tauopathies such as Alzheimer’s disease. |
| first_indexed | 2024-03-09T20:43:43Z |
| format | Article |
| id | doaj.art-6e622c9720bd4e20a6d55d979699fc29 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T20:43:43Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-6e622c9720bd4e20a6d55d979699fc292023-11-23T22:51:03ZengMDPI AGCells2073-44092022-03-0111584010.3390/cells11050840What’s in a Gene? The Outstanding Diversity of <i>MAPT</i>Daniel Ruiz-Gabarre0Almudena Carnero-Espejo1Jesús Ávila2Vega García-Escudero3Anatomy, Histology and Neuroscience Department, School of Medicine, Universidad Autónoma de Madrid (UAM), 28029 Madrid, SpainAnatomy, Histology and Neuroscience Department, School of Medicine, Universidad Autónoma de Madrid (UAM), 28029 Madrid, SpainCentro de Biología Molecular Severo Ochoa (UAM-CSIC), 28049 Madrid, SpainAnatomy, Histology and Neuroscience Department, School of Medicine, Universidad Autónoma de Madrid (UAM), 28029 Madrid, SpainTau protein is a microtubule-associated protein encoded by the <i>MAPT</i> gene that carries out a myriad of physiological functions and has been linked to certain pathologies collectively termed tauopathies, including Alzheimer’s disease, frontotemporal dementia, Huntington’s disease, progressive supranuclear palsy, etc. Alternative splicing is a physiological process by which cells generate several transcripts from one single gene and may in turn give rise to different proteins from the same gene. <i>MAPT</i> transcripts have been proven to be subjected to alternative splicing, generating six main isoforms in the central nervous system. Research throughout the years has demonstrated that the splicing landscape of the <i>MAPT</i> gene is far more complex than that, including at least exon skipping events, the use of 3′ and 5′ alternative splice sites and, as has been recently discovered, also intron retention. In addition, <i>MAPT</i> alternative splicing has been showed to be regulated spatially and developmentally, further evidencing the complexity of the gene’s splicing regulation. It is unclear what would drive the need for the existence of so many isoforms encoded by the same gene, but a wide range of functions have been ascribed to these Tau isoforms, both in physiology and pathology. In this review we offer a comprehensive up-to-date exploration of the mechanisms leading to the outstanding diversity of isoforms expressed from the <i>MAPT</i> gene and the functions in which such isoforms are involved, including their potential role in the onset and development of tauopathies such as Alzheimer’s disease.https://www.mdpi.com/2073-4409/11/5/840<i>MAPT</i>Tau proteinalternative splicingintron retentionAlzheimer’s disease |
| spellingShingle | Daniel Ruiz-Gabarre Almudena Carnero-Espejo Jesús Ávila Vega García-Escudero What’s in a Gene? The Outstanding Diversity of <i>MAPT</i> Cells <i>MAPT</i> Tau protein alternative splicing intron retention Alzheimer’s disease |
| title | What’s in a Gene? The Outstanding Diversity of <i>MAPT</i> |
| title_full | What’s in a Gene? The Outstanding Diversity of <i>MAPT</i> |
| title_fullStr | What’s in a Gene? The Outstanding Diversity of <i>MAPT</i> |
| title_full_unstemmed | What’s in a Gene? The Outstanding Diversity of <i>MAPT</i> |
| title_short | What’s in a Gene? The Outstanding Diversity of <i>MAPT</i> |
| title_sort | what s in a gene the outstanding diversity of i mapt i |
| topic | <i>MAPT</i> Tau protein alternative splicing intron retention Alzheimer’s disease |
| url | https://www.mdpi.com/2073-4409/11/5/840 |
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