Atg16L1, an essential factor for canonical autophagy, participates in hormone secretion from PC12 cells independently of autophagic activity

Ishibashi, Koutaro; Uemura, Takefumi; Waguri, Satoshi; Fukuda, Mitsunori

doi:10.1091/mbc.e12-01-0010

Cited by 63 publications

(57 citation statements)

References 38 publications

(64 reference statements)

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“…Actually, four members of the Rab3 subfamily (Rab3A/B/C/D) are known to have redundant roles in mouse survival (39), and two members of the Rab8 subfamily (Rab8A/B) have compensatory roles in the apical transport of epithelial cells (40). Recent accumulating evidence, however, indicates that the A and B isoforms of Rabs have different functions in certain membrane trafficking events and different subcellular localizations even within the same cell type (41)(42)(43)(44)(45)(46)(47). One good example is the Rab27 subfamily in which Rab27A and Rab27B differently regulate the exocytosis of certain types of lysosome-related organelles, e.g.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Small GTPase Rab2B and Its Specific Binding Protein Golgi-associated Rab2B Interactor-like 4 (GARI-L4) Regulate Golgi Morphology

Aizawa

Fukuda

2015

Journal of Biological Chemistry

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Background: Rab small GTPases are membrane trafficking proteins in eukaryotes. Results: Comprehensive knockdown screening identified six Rab isoforms that are involved in regulating Golgi morphology in HeLa-S3 cells. Conclusion: Five of the six Rabs, including Rab2A and Rab2B, non-redundantly regulate Golgi morphology. A Rab2B-specific effector, GARI-L4, also regulates it. Significance: This is the first study to systematically analyze all human Rabs in the Golgi.

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Section: Discussionmentioning

confidence: 99%

“…One of the candidate Rab subfamilies for involvement in the morphology of the Golgi was the Rab33 subfamily because both Rab33A and Rab33B are present in the Golgi (47,50). However, simultaneous knockdown of both Rab33A and Rab33B had no effect on the Golgi morphology of HeLa-S3 cells (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Small GTPase Rab2B and Its Specific Binding Protein Golgi-associated Rab2B Interactor-like 4 (GARI-L4) Regulate Golgi Morphology

Aizawa

Fukuda

2015

Journal of Biological Chemistry

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“…pMRX-IRES-bsr-HA-ULK1 was similarly produced from pEF-HA-ULK1. 40 The cDNA insert of pEGFP-C1-TBC1D2B and pEF-T7-TBC1D5 20 was also subcloned into the pMRX-IRES-puro-HA vector 38 and pEF-FLAG tag vector. 39 …”

Section: Plasmid Constructionmentioning

confidence: 99%

Differing susceptibility to autophagic degradation of two LC3-binding proteins: SQSTM1/p62 and TBC1D25/OATL1

et al. 2016

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MAP1LC3/LC3 (a mammalian ortholog family of yeast Atg8) is a ubiquitin-like protein that is essential for autophagosome formation. LC3 is conjugated to phosphatidylethanolamine on phagophores and ends up distributed both inside and outside the autophagosome membrane. One of the well-known functions of LC3 is as a binding partner for receptor proteins, which target polyubiquitinated organelles and proteins to the phagophore through direct interaction with LC3 in selective autophagy, and their LC3-binding ability is essential for degradation of the polyubiquitinated substances. Although a number of LC3-binding proteins have been identified, it is unknown whether they are substrates of autophagy or how their interaction with LC3 is regulated. We previously showed that one LC3-binding protein, TBC1D25/OATL1, plays an inhibitory role in the maturation step of autophagosomes and that this function depends on its binding to LC3. Interestingly, TBC1D25 seems not to be a substrate of autophagy, despite being present on the phagophore. In this study we investigated the molecular basis for the escape of TBC1D25 from autophagic degradation by performing a chimeric analysis between TBC1D25 and SQSTM1/p62 (sequestosome 1), and the results showed that mutant TBC1D25 with an intact LC3-binding site can become an autophagic substrate when TBC1D25 is forcibly oligomerized. In addition, an ultrastructural analysis showed that TBC1D25 is mainly localized outside autophagosomes, whereas an oligomerized TBC1D25 mutant rather uniformly resides both inside and outside the autophagosomes. Our findings indicate that oligomerization is a key factor in the degradation of LC3-binding proteins and suggest that lack of oligomerization ability of TBC1D25 results in its asymmetric localization at the outer autophagosome membrane.

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“…In fact, the expression of the active form of Rab33B increased the amount of LC3-II as previously reported [70], but did not show the colocalization of lysosomal membrane protein LAMP-1 with LC3-positive dots [71], suggesting that autophagosomes in the active form of Rab33B-expressing cells cannot efficiently fuse with lysosomes. Very recently, it was revealed that Atg16L interacts with Rab33A and that this interaction is required for the dense-core vesicle localization of Atg16L in neuroendocrine PC12 cells [72]. Knockdown of endogenous Atg16L in PC12 cells caused marked inhibition of hormone secretion independently of autophagic activity [72], indicating that Atg16L controls autophagy in all cell types as well as secretion from dense-core vesicles, presumably by acting as a Rab33A effector, in neuroendocrine cells.…”

Section: Rab33 Gtpase and Autophagymentioning

confidence: 99%

“…Very recently, it was revealed that Atg16L interacts with Rab33A and that this interaction is required for the dense-core vesicle localization of Atg16L in neuroendocrine PC12 cells [72]. Knockdown of endogenous Atg16L in PC12 cells caused marked inhibition of hormone secretion independently of autophagic activity [72], indicating that Atg16L controls autophagy in all cell types as well as secretion from dense-core vesicles, presumably by acting as a Rab33A effector, in neuroendocrine cells.…”

Section: Rab33 Gtpase and Autophagymentioning

confidence: 99%

Rab GTPases in Autophagy

Hirota¹,

Fujimoto²,

Tanaka³

2013

Autophagy - A Double-Edged Sword - Cell Survival or Death?

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Atg16L1, an essential factor for canonical autophagy, participates in hormone secretion from PC12 cells independently of autophagic activity

Cited by 63 publications

References 38 publications

Small GTPase Rab2B and Its Specific Binding Protein Golgi-associated Rab2B Interactor-like 4 (GARI-L4) Regulate Golgi Morphology

Small GTPase Rab2B and Its Specific Binding Protein Golgi-associated Rab2B Interactor-like 4 (GARI-L4) Regulate Golgi Morphology

Differing susceptibility to autophagic degradation of two LC3-binding proteins: SQSTM1/p62 and TBC1D25/OATL1

Rab GTPases in Autophagy

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