Rab7A regulates tau secretion. Issue 4 (29th March 2017)

• Record Type: Journal Article
• Authors: Rodriguez, Lilia; Mohamed, Nguyen‐Vi; Desjardins, Alexandre; Lippé, Roger; Fon, Edward A; Leclerc, Nicole
• Is Part Of: Journal of neurochemistry. Volume 141:Issue 4(2017)
• Page Start: 592
• Page End: 605
• Publication Date: 2017-03-29
• Subjects: Alzheimer's disease -- Rab7A -- secretion -- tau protein; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.13994
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract: The axonal microtubule‐associated protein TAU, involved in Alzheimer's disease (AD), can be found in the extracellular space where it could be taken up by neurons, an event that is believed to contribute to the propagation of tau pathology in the brain. Since the small GTPase Rab7A is involved in the trafficking of endosomes, autophagosomes, and lysosomes, and RAB7A gene expression and protein levels are up‐regulated in AD patients, we tested the hypothesis that Rab7A was involved in tau secretion. We previously reported that both primary cortical neurons and HeLa cells over‐expressing human TAU can release tau. Using these two cellular systems, we demonstrated that Rab7A regulates tau secretion. Upon Rab7A deletion, tau secretion was decreased. Consistent with this, the over‐expression of a dominant negative and a constitutively active form of Rab7A decreased and increased tau secretion, respectively. A partial co‐localization of tau and Rab7‐positive structures in both neurons and HeLa cells indicated that a late endosomal compartment could be involved in its secretion. Collectively, the present data indicate that Rab7A regulates tau secretion and therefore the up‐regulation of RAB7A reported in AD, could contribute to the extracellular accumulation of pathological TAU species that could result in the propagation of tau pathology in the AD brain. Abstract : Our data demonstrate that Rab7A involved in endocytosis and autophagy regulates the secretion of tau protein linked to Alzheimer's disease (AD). The suppression or inactivation of Rab7A decreases tau secretion, whereas the over‐expression of a constitutively active form of Rab7A increases it. tau is found in Rab7‐positive structures indicating that late endosomes could be involved in its secretion. Our data indicate that the up‐regulation of Rab7A noted in AD, could contribute to the release of pathological tau species responsible for the propagation of tau pathology in the AD brain.