title: PIKfyve mediates the motility of late endosomes and lysosomes in neuronal dendrites.
abstract: The endosome/lysosome system in the nervous system is critically important for a variety of neuronal functions such as neurite outgrowth, retrograde transport, and synaptic plasticity. In neurons, the endosome/lysosome system is crucial for the activity-dependent internalization of membrane proteins and contributes to the regulation of lipid level on the plasma membrane. Although homeostasis of membrane dynamics plays important roles in the properties of central nervous systems, it has not been elucidated how endosome/lysosome system is regulated. Here, we report that phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) mediates the motility of late endosomes and lysosomes in neuronal dendrites. Endosomes and lysosomes are highly motile in resting neurons, however knockdown of PIKfyve led to a significant reduction in late endosomes and lysosomes motility. We also found that vesicle acidification is crucial for their motility and PIKfyve is associated with this process indirectly. These data suggest that PIKfyve mediates vesicle motility through the regulation of vesicle integrity in neurons.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan; Department of Neurobiology, Stanford University School of Medicine, Fairchild Research Laboratories D227, 299 Campus Drive, Stanford, CA 94305, USA. Electronic address: tsuruta.fuminori.fn@u.tsukuba.ac.jp.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Tsuruta
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Fairchild Research Laboratories D227, 299 Campus Drive, Stanford, CA 94305, USA.
authors.forename: Ricardo E
authors.initials: RE
authors.lastname: Dolmetsch
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000502:physiology* / Q000648:ultrastructure; D011992:Endosomes / Q000502:physiology*; D006801:Humans; D008247:Lysosomes / Q000502:physiology*; D008813:Mice, Inbred ICR; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics; D017207:Rats, Sprague-Dawley
chemical_list: D034741:RNA, Small Interfering; C544731:PIKfyve protein, rat; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); C116930:Pikfyve protein, mouse
keywords: Late endosome; Lysosome; PIKfyve; PtdIns(3,5)P(2)