title: Formation, release, and internalization of stable tau oligomers in cells.
abstract: Tau is a neuronal microtubule-binding protein that, in Alzheimer's disease and other neurodegenerative diseases, can form oligomeric and large fibrillar aggregates, which deposit in neurofibrillary tangles. Tau's physiological state of multimerization appears to vary across conditions, and a stable dimeric form of soluble tau has been suggested from experiments using recombinant tau in vitro. We tested if tau dimerization or oligomerization, also occurs in cells, and if soluble tau oligomers are relevant for the release and internalization of tau. We developed a sensitive tau split-luciferase assay to show the rapid intracellular formation of stable tau dimers that are released and taken up by cells. Our data further suggest that tau dimerization can be accelerated slightly by aggregation catalysts. We conclude that tau oligomers are a stable physiological form of tau, and that tau oligomerization does not necessarily lead to tau aggregation.
authors.affiliation: Department of Neurology, Massachusetts General Hospital, MassGeneral Institute of Neurodegenerative Diseases (MIND), Charlestown, Massachusetts, USA.|Department of Neurology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Susanne
authors.initials: S
authors.lastname: Wegmann
authors.affiliation: Department of Neurology, Massachusetts General Hospital, MassGeneral Institute of Neurodegenerative Diseases (MIND), Charlestown, Massachusetts, USA.|Department of Neurology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Nicholls
authors.affiliation: Department of Neurology, Massachusetts General Hospital, MassGeneral Institute of Neurodegenerative Diseases (MIND), Charlestown, Massachusetts, USA.|Department of Neurology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Shuko
authors.initials: S
authors.lastname: Takeda
authors.affiliation: Department of Neurology, Massachusetts General Hospital, MassGeneral Institute of Neurodegenerative Diseases (MIND), Charlestown, Massachusetts, USA.|Department of Neurology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Zhanyun
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Department of Neurology, Massachusetts General Hospital, MassGeneral Institute of Neurodegenerative Diseases (MIND), Charlestown, Massachusetts, USA.|Department of Neurology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Hyman
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D016874:Neurofibrillary Tangles / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D055503:Protein Multimerization / Q000502:physiology*; D016875:tau Proteins / Q000378:metabolism* / Q000633:toxicity
chemical_list: D016875:tau Proteins
keywords: Gaussia luciferase assay; dimerization; oligomers; tau protein