ATG9 raises the BAR for PI4P in autophagy

Shatz, Oren; Elazar, Zvulun

doi:10.1083/jcb.201904063

Cited by 5 publications

(2 citation statements)

References 12 publications

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“…The multi-pass transmembrane protein ATG9A traffics through the endocytic network to establish a perinuclear RAB11/TGN-associated compartment from where it can be rapidly mobilised upon autophagy stimulation to form peripheral membrane pools required for efficient autophagosome biogenesis (for a recent discussion, see Shatz and Elazar, 2019 ). Because SNX18 has been found to coordinate ATG9A redistribution during autophagy via the actions of dynamin-2 ( Søreng et al, 2018 ), we tested whether SNX4 also influences ATG9A trafficking during autophagy stimulation.…”

Section: Resultsmentioning

confidence: 99%

A heterodimeric SNX4–SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly

Antón

Betin

Simonetti

et al. 2020

Journal of Cell Science

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The sorting nexins (SNXs) are a family of peripheral membrane proteins that direct protein trafficking decisions within the endocytic network. Emerging evidence in yeast and mammalian cells implicates a subgroup of SNXs in selective and non-selective forms of autophagy. Using siRNA and CRISPR-Cas9, we demonstrate that the SNX-BAR protein SNX4 is needed for efficient LC3 (also known as MAP1LC3) lipidation and autophagosome assembly in mammalian cells. SNX-BARs exist as homo- and hetero-dimers, and we show that SNX4 forms functional heterodimers with either SNX7 or SNX30 that associate with tubulovesicular endocytic membranes. Detailed image-based analysis during the early stages of autophagosome assembly reveals that SNX4–SNX7 is an autophagy-specific SNX-BAR heterodimer, required for efficient recruitment and/or retention of core autophagy regulators at the nascent isolation membrane. SNX4 partially colocalises with juxtanuclear ATG9A-positive membranes, with our data linking the autophagy defect upon SNX4 disruption to the mis-trafficking and/or retention of ATG9A in the Golgi region. Taken together, our findings show that the SNX4–SNX7 heterodimer coordinates ATG9A trafficking within the endocytic network to establish productive autophagosome assembly sites, thus extending knowledge of SNXs as positive regulators of autophagy.

show abstract

Section: Resultsmentioning

confidence: 99%

A heterodimeric SNX4–SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly

Antón

Betin

Simonetti

et al. 2020

Journal of Cell Science

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show abstract

“…The multi-pass transmembrane protein ATG9A traffics through the endocytic network to establish a perinuclear RAB11/TGN-associated compartment from where it can be rapidly mobilised upon autophagy stimulation to form peripheral membrane pools required for efficient autophagosome biogenesis (for a recent discussion, see (Shatz and Elazar, 2019)). Since SNX18 has been found to coordinate ATG9A redistribution during autophagy via the actions of dynamin-2 (Soreng et al, 2018), we tested whether SNX4 also influences ATG9A trafficking during autophagy stimulation.…”

Section: Atg9a Trafficking Is Defective In Snx4 Crispr Knockout (Ko) mentioning

confidence: 99%

A heterodimeric SNX4:SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly

Antón

Betin

Simonetti

et al. 2020

Preprint

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STATEMENT: A heterodimeric SNX4:SNX7 SNX-BAR complex regulates mammalian autophagosome assembly through the control of ATG9 trafficking. ABSTRACTEfficient mammalian autophagosome biogenesis requires coordinated input from other cellular endomembrane compartments. Such coordination includes the stimulated trafficking to autophagosome assembly sites of the essential autophagy proteins, ATG9 and ATG16L1, via distinct endosomal compartments. Protein trafficking within the endocytic network is directed by a conserved family of sorting nexins (SNXs), with previous studies implicating SNX18 (an SH3 domain-type SNX-BAR protein) in the mobilisation of ATG9A and ATG16L1 from recycling endosomes during autophagy. Using siRNA and CRISPR-Cas9, we demonstrate that a second mammalian SNX-BAR, SNX4, is needed for efficient LC3 lipidation and autophagosome assembly in mammalian cells. SNX-BARs exist as homo-and heterodimers, and we show that SNX4 forms functional heterodimers with either SNX7 or SNX30, and that these associate with tubulovesicular endocytic membranes at steady state. Detailed image-based analysis during the early stages of autophagosome assembly reveal that SNX4:SNX7 is the autophagyspecific heterodimeric SNX-BAR complex, required for efficient recruitment/retention of core autophagy regulators at the nascent isolation membrane. SNX4 partially co-localises with juxtanuclear ATG9Apositive membranes, with our data linking the SNX4 autophagy defect to the mis-trafficking and/or retention of ATG9A in the Golgi region. Together, our findings show that the SNX4:SNX7 heterodimer coordinates ATG9A trafficking within the endocytic network to establish productive autophagosome assembly sites.

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Redox balance and autophagy regulation in cancer progression and their therapeutic perspective

et al. 2022

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ATG9 raises the BAR for PI4P in autophagy

Abstract: Shatz and Elazar discuss a recent study from Judith et al. demonstrating how ATG9A vesicles drive early autophagy.

Cited by 5 publications

References 12 publications

A heterodimeric SNX4–SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly

A heterodimeric SNX4–SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly

A heterodimeric SNX4:SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly

Redox balance and autophagy regulation in cancer progression and their therapeutic perspective

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ATG9 raises the BAR for PI4P in autophagy

Abstract: Shatz and Elazar discuss a recent study from Judith et al. demonstrating how ATG9A vesicles drive early autophagy.

Cited by 5 publications

References 12 publications

A heterodimeric SNX4­–SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly

A heterodimeric SNX4­–SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly

A heterodimeric SNX4:SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly

Redox balance and autophagy regulation in cancer progression and their therapeutic perspective

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A heterodimeric SNX4–SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly

A heterodimeric SNX4–SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly