Axodendritic targeting of TAU and MAP2 and microtubule polarization in iPSC-derived versus SH-SY5Y-derived human neurons
Cell polarity is crucial in neurons, characterized by distinct axonal and dendritic structures. Neurons generally have one long axon and multiple shorter dendrites, marked by specific microtubule (MT)-associated proteins, e.g., MAP2 for dendrites and TAU for axons, while the scaffolding proteins Ank...
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De Gruyter
2024-12-01
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| Series: | Open Life Sciences |
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| Online Access: | https://doi.org/10.1515/biol-2022-1010 |
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| author | Breuer Helen Bell-Simons Michael Zempel Hans |
| author_facet | Breuer Helen Bell-Simons Michael Zempel Hans |
| author_sort | Breuer Helen |
| collection | DOAJ |
| description | Cell polarity is crucial in neurons, characterized by distinct axonal and dendritic structures. Neurons generally have one long axon and multiple shorter dendrites, marked by specific microtubule (MT)-associated proteins, e.g., MAP2 for dendrites and TAU for axons, while the scaffolding proteins AnkG and TRIM46 mark the axon-initial-segment. In tauopathies, such as Alzheimer’s disease (AD), TAU sorting, and neuronal polarity are disrupted, leading to MT loss. However, modeling and studying MTs in human neuronal cells relevant to the study of AD and TAU-related neurodegenerative diseases (NDD) is challenging. To study MT dynamics in human neurons, we compared two cell culture systems: SH-SY5Y-derived neurons (SHN) and induced pluripotent stem cell-derived neurons (iN). Using immunostaining and EB3-tdTomato time-lapse imaging, we found AnkG absent in SHN but present in iN, while TRIM46 was present in both. TAU and MAP2 showed axonal and dendritic enrichment, respectively, similar to mouse primary neurons. Both neuron types exhibited polarized MT structures, with unidirectional MTs in axons and bidirectional MTs in dendrites. Polymerization speeds were similar; however, iNs had more retrograde MT growth events, while SHN showed a higher overall number of growth events. Thus, SHN and iN are both suitable for studying neuronal cell polarity, with SHN being particularly suitable if the focus is not the AIS. |
| format | Article |
| id | doaj-art-63b5ac23f68e4fd2870f2c98d99a941f |
| institution | Kabale University |
| issn | 2391-5412 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | De Gruyter |
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| series | Open Life Sciences |
| spelling | doaj-art-63b5ac23f68e4fd2870f2c98d99a941f2025-01-07T07:55:32ZengDe GruyterOpen Life Sciences2391-54122024-12-01191667010.1515/biol-2022-1010Axodendritic targeting of TAU and MAP2 and microtubule polarization in iPSC-derived versus SH-SY5Y-derived human neuronsBreuer Helen0Bell-Simons Michael1Zempel Hans2Institute of Human Genetics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 34, 50931, Cologne, GermanyInstitute of Human Genetics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 34, 50931, Cologne, GermanyInstitute of Human Genetics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 34, 50931, Cologne, GermanyCell polarity is crucial in neurons, characterized by distinct axonal and dendritic structures. Neurons generally have one long axon and multiple shorter dendrites, marked by specific microtubule (MT)-associated proteins, e.g., MAP2 for dendrites and TAU for axons, while the scaffolding proteins AnkG and TRIM46 mark the axon-initial-segment. In tauopathies, such as Alzheimer’s disease (AD), TAU sorting, and neuronal polarity are disrupted, leading to MT loss. However, modeling and studying MTs in human neuronal cells relevant to the study of AD and TAU-related neurodegenerative diseases (NDD) is challenging. To study MT dynamics in human neurons, we compared two cell culture systems: SH-SY5Y-derived neurons (SHN) and induced pluripotent stem cell-derived neurons (iN). Using immunostaining and EB3-tdTomato time-lapse imaging, we found AnkG absent in SHN but present in iN, while TRIM46 was present in both. TAU and MAP2 showed axonal and dendritic enrichment, respectively, similar to mouse primary neurons. Both neuron types exhibited polarized MT structures, with unidirectional MTs in axons and bidirectional MTs in dendrites. Polymerization speeds were similar; however, iNs had more retrograde MT growth events, while SHN showed a higher overall number of growth events. Thus, SHN and iN are both suitable for studying neuronal cell polarity, with SHN being particularly suitable if the focus is not the AIS.https://doi.org/10.1515/biol-2022-1010neuronal cell polarityeb3-traffickingdendriteaxon-initial-segmentankg/trim46 |
| spellingShingle | Breuer Helen Bell-Simons Michael Zempel Hans Axodendritic targeting of TAU and MAP2 and microtubule polarization in iPSC-derived versus SH-SY5Y-derived human neurons Open Life Sciences neuronal cell polarity eb3-trafficking dendrite axon-initial-segment ankg/trim46 |
| title | Axodendritic targeting of TAU and MAP2 and microtubule polarization in iPSC-derived versus SH-SY5Y-derived human neurons |
| title_full | Axodendritic targeting of TAU and MAP2 and microtubule polarization in iPSC-derived versus SH-SY5Y-derived human neurons |
| title_fullStr | Axodendritic targeting of TAU and MAP2 and microtubule polarization in iPSC-derived versus SH-SY5Y-derived human neurons |
| title_full_unstemmed | Axodendritic targeting of TAU and MAP2 and microtubule polarization in iPSC-derived versus SH-SY5Y-derived human neurons |
| title_short | Axodendritic targeting of TAU and MAP2 and microtubule polarization in iPSC-derived versus SH-SY5Y-derived human neurons |
| title_sort | axodendritic targeting of tau and map2 and microtubule polarization in ipsc derived versus sh sy5y derived human neurons |
| topic | neuronal cell polarity eb3-trafficking dendrite axon-initial-segment ankg/trim46 |
| url | https://doi.org/10.1515/biol-2022-1010 |
| work_keys_str_mv | AT breuerhelen axodendritictargetingoftauandmap2andmicrotubulepolarizationinipscderivedversusshsy5yderivedhumanneurons AT bellsimonsmichael axodendritictargetingoftauandmap2andmicrotubulepolarizationinipscderivedversusshsy5yderivedhumanneurons AT zempelhans axodendritictargetingoftauandmap2andmicrotubulepolarizationinipscderivedversusshsy5yderivedhumanneurons |