Soluble 4R0N Tau Abrogates Endocytic Vesicular Dynamics

Mahendran, TS and Suresh, SN and Garimella, L and Manjithaya, R (2020) Soluble 4R0N Tau Abrogates Endocytic Vesicular Dynamics. In: Frontiers in Aging Neuroscience, 12 .

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Abstract

Aggregated tau is a hallmark neuropathological feature in numerous neurodegenerative disorders. Previous studies aiming to validate aggregated tau pathology as a pathogenic driver of neurodegeneration in correlation to characteristic behavioral phenotypes have had shortcomings. Although studies on soluble tau pathology have effectively addressed these shortcomings, the role of soluble tau in the molecular pathogenesis of neurodegeneration is not yet unequivocally established. In sporadic Alzheimer�s disease (AD), the relevance of soluble tau pathology in endolysosomal dysfunction and autophagic stress, some of the earliest disease manifestations, is unclear. In this study, we report that soluble 4R0N tau overexpression affects the expression levels of certain markers associated with the endolysosomal system and autophagy. Moreover, through live-cell imaging, we found that the vesicular dynamics of early endosomes were affected with respect to spatiotemporal parameters and vesicle maturation. Additionally, we observed the localization of amyloid precursor protein (APP) along the endocytic pathway and found that upon overexpression of soluble 4R0N tau, APP was preferentially localized to the endocytic compartments implicated in the amyloidogenic pathway. Overall, our observations indicate that soluble 4R0N tau abrogates the dynamics of the endolysosomal system, autophagy, and affects the trafficking of APP. Since the amyloidogenic processing of APP occurs during its progression through the endocytic pathway, our results suggest that the generation of amyloid-β (Aβ) might also be modulated. © Copyright © 2020 Mahendran, Suresh, Garimella and Manjithaya.

Item Type:	Journal Article
Publication:	Frontiers in Aging Neuroscience
Publisher:	Frontiers Media S.A.
Additional Information:	The copyright of this article belongs to Frontiers Media S.A.
Department/Centre:	Autonomous Societies / Centres > Centre for Brain Research
Date Deposited:	22 Jan 2021 09:27
Last Modified:	22 Jan 2021 09:27
URI:	http://eprints.iisc.ac.in/id/eprint/67318

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