Atg16L1 Protein Regulates Hormone Secretion Independent of Autophagy

Koutaro Ishibashi, Mitsunori Fukuda

    Research output: Chapter in Book/Report/Conference proceedingChapter

    Abstract

    Atg16L1 is an essential factor for canonical autophagy, a conserved bulk degradation system in all eukaryotes. Atg16L1 forms a complex with Atg12-conjugated Atg5, i.e., an Atg16L1-5-12 complex, and promotes elongation of isolation membranes possibly by recruiting LC3 and by facilitating its lipidation. Because of its critical role in canonical autophagy, cells from Atg16L1-deficient mice exhibit complete loss of autophagosome formation. Interestingly, the intestinal Paneth cells of Atg16L1-deficient mice exhibit a secretion defect, but the mechanism by which Atg16L1 regulates the secretory pathway is poorly understood. We recently reported the finding that Atg16L1 localizes on hormone-containing dense-core vesicles in neuroendocrine PC12 cells independent of canonical autophagy and that small GTPase Rab33A recruits the Atg16L1-5-12 complex to dense-core vesicles. We also found that knockdown of Atg16L1 in PC12 cells caused a dramatic reduction in hormone secretion independent of the autophagic activity of the cells. Our findings indicate that, in addition to its role in autophagy, Atg16L1 (or the Atg16L1-5-12 complex) regulates hormone secretion from dense-core vesicles, most likely by acting as a Rab33A effector in particular cell types, including PC12 cells.

    Original languageEnglish
    Title of host publicationRole of Autophagy in Therapeutic Applications
    PublisherElsevier Inc.
    Pages103-113
    Number of pages11
    Volume7
    ISBN (Electronic)9780128010525
    ISBN (Print)9780128010433
    DOIs
    Publication statusPublished - 2015 Feb 18

    Keywords

    • Atg16L1
    • Atg16L1-5-12 complex
    • Autophagy
    • Canonical autophagy
    • Crohn's disease

    ASJC Scopus subject areas

    • Immunology and Microbiology(all)

    Fingerprint Dive into the research topics of 'Atg16L1 Protein Regulates Hormone Secretion Independent of Autophagy'. Together they form a unique fingerprint.

    Cite this