title: Rab7A regulates tau secretion.
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.
authors.affiliation: Research Center of the University of Montreal Hospital (CRCHUM), Montréal, Québec, Canada.|CNS Research Group (GRSNC), Montreal, Québec, Canada.|Département de Neurosciences, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Lilia
authors.identifier: 0000-0002-5863-3180
authors.initials: L
authors.lastname: Rodriguez
authors.affiliation: Research Center of the University of Montreal Hospital (CRCHUM), Montréal, Québec, Canada.|CNS Research Group (GRSNC), Montreal, Québec, Canada.|Département de Neurosciences, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Nguyen-Vi
authors.initials: NV
authors.lastname: Mohamed
authors.affiliation: Research Center of the University of Montreal Hospital (CRCHUM), Montréal, Québec, Canada.|CNS Research Group (GRSNC), Montreal, Québec, Canada.|Département de Neurosciences, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Desjardins
authors.affiliation: Département de pathologie et biologie cellulaire, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Roger
authors.initials: R
authors.lastname: Lippé
authors.affiliation: McGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montréal, Québec, Canada.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Fon
authors.affiliation: Research Center of the University of Montreal Hospital (CRCHUM), Montréal, Québec, Canada.|CNS Research Group (GRSNC), Montreal, Québec, Canada.|Département de Neurosciences, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Nicole
authors.identifier: 0000-0002-2678-0020
authors.initials: N
authors.lastname: Leclerc
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D017353:Gene Deletion; D006367:HeLa Cells; D006801:Humans; D009474:Neurons / Q000378:metabolism; D061251:Primary Cell Culture; D034741:RNA, Small Interfering; D015854:Up-Regulation; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000090802:rab7 GTP-Binding Proteins; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; D016875:tau Proteins; D020691:rab GTP-Binding Proteins
keywords: Alzheimer's disease; Rab7A; secretion; tau protein