Differential Effects of the Six Human TAU Isoforms: Somatic Retention of 2N-TAU and Increased Microtubule Number Induced by 4R-TAU
In the adult human brain, six isoforms of the microtubule-associated protein TAU are expressed, which result from alternative splicing of exons 2, 3, and 10 of the MAPT gene. These isoforms differ in the number of N-terminal inserts (0N, 1N, 2N) and C-terminal repeat domains (3R or 4R) and are diffe...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-05-01
|
| Series: | Frontiers in Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2021.643115/full |
| _version_ | 1818361666207744000 |
|---|---|
| author | Sarah Bachmann Sarah Bachmann Michael Bell Michael Bell Jennifer Klimek Jennifer Klimek Hans Zempel Hans Zempel |
| author_facet | Sarah Bachmann Sarah Bachmann Michael Bell Michael Bell Jennifer Klimek Jennifer Klimek Hans Zempel Hans Zempel |
| author_sort | Sarah Bachmann |
| collection | DOAJ |
| description | In the adult human brain, six isoforms of the microtubule-associated protein TAU are expressed, which result from alternative splicing of exons 2, 3, and 10 of the MAPT gene. These isoforms differ in the number of N-terminal inserts (0N, 1N, 2N) and C-terminal repeat domains (3R or 4R) and are differentially expressed depending on the brain region and developmental stage. Although all TAU isoforms can aggregate and form neurofibrillary tangles, some tauopathies, such as Pick’s disease and progressive supranuclear palsy, are characterized by the accumulation of specific TAU isoforms. The influence of the individual TAU isoforms in a cellular context, however, is understudied. In this report, we investigated the subcellular localization of the human-specific TAU isoforms in primary mouse neurons and analyzed TAU isoform-specific effects on cell area and microtubule dynamics in human SH-SY5Y neuroblastoma cells. Our results show that 2N-TAU isoforms are particularly retained from axonal sorting and that axonal enrichment is independent of the number of repeat domains, but that the additional repeat domain of 4R-TAU isoforms results in a general reduction of cell size and an increase of microtubule counts in cells expressing these specific isoforms. Our study points out that individual TAU isoforms may influence microtubule dynamics differentially both by different sorting patterns and by direct effects on microtubule dynamics. |
| first_indexed | 2024-12-13T21:20:18Z |
| format | Article |
| id | doaj.art-c9d1642779794c9d8d32888464acdd0d |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-13T21:20:18Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-c9d1642779794c9d8d32888464acdd0d2022-12-21T23:31:09ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2021-05-011510.3389/fnins.2021.643115643115Differential Effects of the Six Human TAU Isoforms: Somatic Retention of 2N-TAU and Increased Microtubule Number Induced by 4R-TAUSarah Bachmann0Sarah Bachmann1Michael Bell2Michael Bell3Jennifer Klimek4Jennifer Klimek5Hans Zempel6Hans Zempel7Institute of Human Genetics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyCenter for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyInstitute of Human Genetics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyCenter for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyInstitute of Human Genetics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyCenter for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyInstitute of Human Genetics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyCenter for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyIn the adult human brain, six isoforms of the microtubule-associated protein TAU are expressed, which result from alternative splicing of exons 2, 3, and 10 of the MAPT gene. These isoforms differ in the number of N-terminal inserts (0N, 1N, 2N) and C-terminal repeat domains (3R or 4R) and are differentially expressed depending on the brain region and developmental stage. Although all TAU isoforms can aggregate and form neurofibrillary tangles, some tauopathies, such as Pick’s disease and progressive supranuclear palsy, are characterized by the accumulation of specific TAU isoforms. The influence of the individual TAU isoforms in a cellular context, however, is understudied. In this report, we investigated the subcellular localization of the human-specific TAU isoforms in primary mouse neurons and analyzed TAU isoform-specific effects on cell area and microtubule dynamics in human SH-SY5Y neuroblastoma cells. Our results show that 2N-TAU isoforms are particularly retained from axonal sorting and that axonal enrichment is independent of the number of repeat domains, but that the additional repeat domain of 4R-TAU isoforms results in a general reduction of cell size and an increase of microtubule counts in cells expressing these specific isoforms. Our study points out that individual TAU isoforms may influence microtubule dynamics differentially both by different sorting patterns and by direct effects on microtubule dynamics.https://www.frontiersin.org/articles/10.3389/fnins.2021.643115/fullTAUMAPTmicrotubule-associated proteinsmicrotubule dynamicsprimary neuron cell cultureSH-SY5Y cell line |
| spellingShingle | Sarah Bachmann Sarah Bachmann Michael Bell Michael Bell Jennifer Klimek Jennifer Klimek Hans Zempel Hans Zempel Differential Effects of the Six Human TAU Isoforms: Somatic Retention of 2N-TAU and Increased Microtubule Number Induced by 4R-TAU Frontiers in Neuroscience TAU MAPT microtubule-associated proteins microtubule dynamics primary neuron cell culture SH-SY5Y cell line |
| title | Differential Effects of the Six Human TAU Isoforms: Somatic Retention of 2N-TAU and Increased Microtubule Number Induced by 4R-TAU |
| title_full | Differential Effects of the Six Human TAU Isoforms: Somatic Retention of 2N-TAU and Increased Microtubule Number Induced by 4R-TAU |
| title_fullStr | Differential Effects of the Six Human TAU Isoforms: Somatic Retention of 2N-TAU and Increased Microtubule Number Induced by 4R-TAU |
| title_full_unstemmed | Differential Effects of the Six Human TAU Isoforms: Somatic Retention of 2N-TAU and Increased Microtubule Number Induced by 4R-TAU |
| title_short | Differential Effects of the Six Human TAU Isoforms: Somatic Retention of 2N-TAU and Increased Microtubule Number Induced by 4R-TAU |
| title_sort | differential effects of the six human tau isoforms somatic retention of 2n tau and increased microtubule number induced by 4r tau |
| topic | TAU MAPT microtubule-associated proteins microtubule dynamics primary neuron cell culture SH-SY5Y cell line |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2021.643115/full |
| work_keys_str_mv | AT sarahbachmann differentialeffectsofthesixhumantauisoformssomaticretentionof2ntauandincreasedmicrotubulenumberinducedby4rtau AT sarahbachmann differentialeffectsofthesixhumantauisoformssomaticretentionof2ntauandincreasedmicrotubulenumberinducedby4rtau AT michaelbell differentialeffectsofthesixhumantauisoformssomaticretentionof2ntauandincreasedmicrotubulenumberinducedby4rtau AT michaelbell differentialeffectsofthesixhumantauisoformssomaticretentionof2ntauandincreasedmicrotubulenumberinducedby4rtau AT jenniferklimek differentialeffectsofthesixhumantauisoformssomaticretentionof2ntauandincreasedmicrotubulenumberinducedby4rtau AT jenniferklimek differentialeffectsofthesixhumantauisoformssomaticretentionof2ntauandincreasedmicrotubulenumberinducedby4rtau AT hanszempel differentialeffectsofthesixhumantauisoformssomaticretentionof2ntauandincreasedmicrotubulenumberinducedby4rtau AT hanszempel differentialeffectsofthesixhumantauisoformssomaticretentionof2ntauandincreasedmicrotubulenumberinducedby4rtau |