Universität zu Köln

Bachmann, Sarah ORCID: 0000-0002-3636-1364, Bell, Michael, Klimek, Jennifer and Zempel, Hans (2021). Differential Effects of the Six Human TAU Isoforms: Somatic Retention of 2N-TAU and Increased Microtubule Number Induced by 4R-TAU. Front. Neurosci., 15. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1662-453X

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bachmann, Sarah UNSPECIFIED orcid.org/0000-0002-3636-1364 UNSPECIFIED Bell, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Klimek, Jennifer UNSPECIFIED UNSPECIFIED UNSPECIFIED Zempel, Hans UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-561631
DOI:	10.3389/fnins.2021.643115
Journal or Publication Title:	Front. Neurosci.
Volume:	15
Date:	2021
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1662-453X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROGRESSIVE SUPRANUCLEAR PALSY; EXPRESSION; PROTEIN; BINDING; PLATFORM; NEURONS; GROWTH; REGION; BRAIN; ONSET Multiple languages Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/56163