title: The lipid kinase PI4KIIIβ preserves lysosomal identity.
abstract: Lipid modifications are essential in cellular sorting and trafficking inside cells. The role of phosphoinositides in trafficking between Golgi and endocytic/lysosomal compartments has been extensively explored and the kinases responsible for these lipid changes have been identified. In contrast, the mechanisms that mediate exit and recycling from lysosomes (Lys), considered for a long time as terminal compartments, are less understood. In this work, we identify a dynamic association of the lipid kinase PI4KIIIβ with Lys and unveil its regulatory function in lysosomal export and retrieval. We have found that absence of PI4KIIIβ leads to abnormal formation of tubular structures from the lysosomal surface and loss of lysosomal constituents through these tubules. We demonstrate that the kinase activity of PI4KIIIβ is necessary to prevent this unwanted lysosomal efflux under normal conditions, and to facilitate proper sorting when recycling of lysosomal material is needed, such as in the physiological context of lysosomal reformation after prolonged starvation.
authors.affiliation: Department of Development and Molecular Biology, Bronx, NY 10461, USA.
authors.forename: Sunandini
authors.initials: S
authors.lastname: Sridhar
authors.forename: Bindi
authors.initials: B
authors.lastname: Patel
authors.forename: David
authors.initials: D
authors.lastname: Aphkhazava
authors.forename: Fernando
authors.initials: F
authors.lastname: Macian
authors.forename: Laura
authors.initials: L
authors.lastname: Santambrogio
authors.forename: Dennis
authors.initials: D
authors.lastname: Shields
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Cuervo
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D019556:COS Cells; D002522:Chlorocebus aethiops; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D016086:Lentivirus; D050356:Lipid Metabolism; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism* / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D020033:Protein Isoforms / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D052118:Lysosomal-Associated Membrane Protein 1; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D019870:1-Phosphatidylinositol 4-Kinase