The lipid kinase PI4KIIIβ preserves lysosomal identity

Sunandini Sridhar, Bindi Patel, David Aphkhazava, Fernando Macian, Laura Santambrogio, Dennis Shields, Ana Maria Cuervo

Research output: Contribution to journalArticle

67 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)324-339
Number of pages16
JournalEMBO Journal
Volume32
Issue number3
DOIs
StatePublished - Feb 6 2013

Keywords

  • Autophagy
  • Lipid kinase
  • Lysosome membrane
  • Vesicular trafficking

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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  • Cite this

    Sridhar, S., Patel, B., Aphkhazava, D., Macian, F., Santambrogio, L., Shields, D., & Cuervo, A. M. (2013). The lipid kinase PI4KIIIβ preserves lysosomal identity. EMBO Journal, 32(3), 324-339. https://doi.org/10.1038/emboj.2012.341