title: α-synuclein transfer through tunneling nanotubes occurs in SH-SY5Y cells and primary brain pericytes from Parkinson's disease patients.
abstract: Parkinson's disease (PD) is characterized by the presence of inclusions known as Lewy bodies, which mainly consist of α-synuclein (α-syn) aggregates. There is growing evidence that α-syn self-propagates in non-neuronal cells, thereby contributing to the progression and spread of PD pathology in the brain. Tunneling nanotubes (TNTs) are long, thin, F-actin-based membranous channels that connect cells and have been proposed to act as conduits for α-syn transfer between cells. SH-SY5Y cells and primary human brain pericytes, derived from postmortem PD brains, frequently form TNTs that allow α-syn transfer and long-distance electrical coupling between cells. Pericytes in situ contain α-syn precipitates like those seen in neurons. Exchange through TNTs was rapid, but dependent on the size of the protein. Proteins were able to spread throughout a network of cells connected by TNTs. Transfer through TNTs was not restricted to α-syn; fluorescent control proteins and labeled membrane were also exchanged through TNTs. Most importantly the formation of TNTs and transfer continued during mitosis. Together, our results provide a detailed description of TNTs in SH-SY5Y cells and human brain PD pericytes, demonstrating their role in α-syn transfer and further emphasize the importance that non-neuronal cells, such as pericytes play in disease progression.
authors.affiliation: Department of Anatomy and Medical Imaging, Faculty of Medical and Health Science, University of Auckland, Private Bag 92019, Auckland, New Zealand.|Centre for Brain Research, Faculty of Medical and Health Science, University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: Birger Victor
authors.initials: BV
authors.lastname: Dieriks
authors.affiliation: Centre for Brain Research, Faculty of Medical and Health Science, University of Auckland, Private Bag 92019, Auckland, New Zealand.|Department of Pharmacology, Faculty of Medical and Health Science, University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: Thomas I-H
authors.initials: TI
authors.lastname: Park
authors.affiliation: Centre for Brain Research, Faculty of Medical and Health Science, University of Auckland, Private Bag 92019, Auckland, New Zealand.|Department of Physiology, Faculty of Medical and Health Science, University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: Chantelle
authors.initials: C
authors.lastname: Fourie
authors.affiliation: Department of Anatomy and Medical Imaging, Faculty of Medical and Health Science, University of Auckland, Private Bag 92019, Auckland, New Zealand.|Centre for Brain Research, Faculty of Medical and Health Science, University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: Richard L M
authors.initials: RL
authors.lastname: Faull
authors.affiliation: Centre for Brain Research, Faculty of Medical and Health Science, University of Auckland, Private Bag 92019, Auckland, New Zealand.|Department of Pharmacology, Faculty of Medical and Health Science, University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: Mike
authors.initials: M
authors.lastname: Dragunow
authors.affiliation: Department of Anatomy and Medical Imaging, Faculty of Medical and Health Science, University of Auckland, Private Bag 92019, Auckland, New Zealand.|Centre for Brain Research, Faculty of Medical and Health Science, University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: Maurice A
authors.initials: MA
authors.lastname: Curtis
mesh_terms: D001921:Brain / Q000166:cytology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D016631:Lewy Bodies / Q000378:metabolism; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D008938:Mitosis; D043942:Nanotubes / Q000737:chemistry*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology*; D020286:Pericytes / Q000166:cytology / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology*; D059008:Time-Lapse Imaging; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein