Axonal TAU Sorting Requires the C-terminus of TAU but is Independent of ANKG and TRIM46 Enrichment at the AIS
| Autor: | Hans Zempel, Michael Bell, Jennifer Klimek, Sarah Bachmann, Felix Langerscheidt |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Ankyrins
0301 basic medicine Tau protein Cell Nerve Tissue Proteins tau Proteins Endogeny Biology Mice 03 medical and health sciences 0302 clinical medicine Cell Line Tumor medicine Animals Humans Ankyrin Axon Axon Initial Segment Neurons chemistry.chemical_classification General Neuroscience Wild type Transfection Axon initial segment Axons Cell biology Protein Transport 030104 developmental biology medicine.anatomical_structure nervous system chemistry biology.protein Neuron Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Neuroscience. 461:155-171 |
| ISSN: | 0306-4522 |
| DOI: | 10.1016/j.neuroscience.2021.01.041 |
| Popis: | Somatodendritic missorting of the axonal protein TAU is a hallmark of Alzheimer’s disease and related tauopathies. Cultured rodent primary neurons and iPSC-derived neurons are used for studying mechanisms of neuronal polarity, including TAU trafficking. However, these models are expensive, time-consuming and/or require the sacrification of animals. In this study, we evaluated four differentiation procedures to generate mature neuron cultures from human SH-SY5Y neuroblastoma cells, in comparison to mouse primary neurons, and tested their TAU sorting capacity. We show that SH-SY5Y-derived neurons, differentiated with sequential RA/BDNF treatment, are suitable for investigating axonal TAU sorting. These human neurons show pronounced neuronal polarity, axodendritic outgrowth, expression of the neuronal maturation markers TAU and MAP2, and, importantly, efficient axonal sorting of endogenous and transfected human wild type TAU, similar to primary neurons. We demonstrate that axonal TAU enrichment requires the presence of the C-terminal half, as a C-terminus-lacking construct (N-term-TAUHA) is not axonally enriched in both neuronal cell models. Moreover, SH-SY5Y-derived neurons do not show formation of a classical axon initial segment (AIS), indicated by the lack of Ankyrin G (ANKG) and tripartite motif-containing protein 46 (TRIM46) at the proximal axon, which suggests that successful axonal TAU sorting is independent of classical AIS formation. Taken together, our results suggest i) that SH-SY5Y-derived neurons are a valuable human neuronal cell model for studying TAU sorting, which is readily accessible at low cost and without animal need, and that ii) the mechanisms of axonal TAU targeting require the TAU C-terminal half but are independent of ANKG or TRIM46 enrichment at the proximal axon. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect