ATG9A shapes the forming autophagosome through Arfaptin 2 and phosphatidylinositol 4-kinase IIIβ

Judith, Delphine; Jefferies, Harold B.J.; Boeing, Stefan; Frith, David; Snijders, Ambrosius P.; Tooze, Sharon A.

doi:10.1083/jcb.201901115

Cited by 171 publications

(214 citation statements)

References 55 publications

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“…Application of this threshold also predicted ATG9A and Furin, normally resident in Golgi membranes and endosomes, as vesicle cargo specifically captured by golgin-97-mito ( Fig. 1E) (12,13). We verified this by immunofluorescence ( Fig.…”

Section: Lopit-dc On Mitochondrial Relocated Golgin-97 and Gcc88supporting

confidence: 53%

“…This strongly suggests that ATG9A and SERINC1 are on retrograde vesicles derived from an, as yet, undefined sorting pathway. ATG9A is an important regulator of autophagosome formation and SERINC proteins have recently been identified as HIV restriction factors (13,22,23). Thus, their relocation to mitochondria by golgin-97mito could provide a powerful assay to study the pathology of these proteins in the future.…”

Section: Cargo Specific To Golgin-97 and Golgin-245mentioning

confidence: 99%

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Determining the content of vesicles captured by golgin tethers using LOPIT-DC

Shin

Crook²,

Borgeaud

et al. 2019

Preprint

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The internal organisation of the cell depends on tethers at destination organelles to selectively capture incoming transport vesicles to facilitate SNARE-mediated fusion. The golgin long coiledcoil proteins function as tethers that contributes to this specificity at the Golgi (1). Golgin-97, golgin-245 and GCC88 golgins of the trans-Golgi capture vesicles derived from endosomes, which serve to recycle the critical Golgi machinery required to deliver lysosomal hydrolases and to maintain exocytosis. Retrograde trafficking from endosomes to the trans-Golgi network (TGN) is a complex process that involves the sorting of transmembrane cargo proteins into distinct transport vesicles by adaptors from multiple pathways. The content of these distinct vesicles, which golgin they target and the factors that mediate this targeting are not well understood. The major challenges that have limited advances in these areas is the transient nature of vesicle tethering, and the redundancies in their mechanisms that confound experimental dissection. To gain better insight into these problems, we performed organelle proteomics using the Localisation of Organelle Proteins by Isotope Tagging after Differential ultraCentrifugation (LOPIT-DC) method on a system in which an ectopic golgin causes vesicles to accumulate in a tethered state (2). By incorporating Bayesian statistical modelling into our analysis (3), we determined that over 45 transmembrane proteins and 51 peripheral membrane proteins of the endosomal network are on vesicles captured by golgin-97, including known cargo and components of the clathrin/AP-1, retromer-dependent and -independent transport pathways. We also determined a distinct class of vesicles shared by golgin-97, golgin-245 and GCC88 that is enriched in TMEM87A, a multi-pass transmembrane protein of unknown function that has previously been implicated in endosome-to-Golgi retrograde transport (4). Finally, we categorically demonstrate that the vesicles that these golgins capture are retrograde transport vesicles based on the lack of enrichment of lysosomal hydrolases in our LOPIT-DC data, and from correlative light electron tomography images of spherical vesicles captured by golgin-97. Together, our study demonstrates the power of combining LOPIT-DC with Bayesian statistical analysis in interrogating the dynamic spatial movement of proteins in transport vesicles.

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Section: Lopit-dc On Mitochondrial Relocated Golgin-97 and Gcc88supporting

confidence: 53%

Section: Cargo Specific To Golgin-97 and Golgin-245mentioning

confidence: 99%

Determining the content of vesicles captured by golgin tethers using LOPIT-DC

Shin

Crook²,

Borgeaud

et al. 2019

Preprint

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“…The evidence that the GC is a membrane source for phagophore expansion comes from the fact that ATG9 is the only transmembrane protein of the core autophagy machinery that is required for autophagosome formation, although its incorporation into mature autophagosomes is debated. ATG9 has not been clearly localized on mature autophagosomes in mammalian cells, whereas it is retained and localized to mature autophagosomes in yeast . In feeding conditions, ATG9 shows perinuclear localization, partially overlapping with medial‐ and trans‐Golgi (Fig.…”

Section: Golgi Complex Roles In Autophagosome Biogenesis and Maturationmentioning

confidence: 95%

“…Together, these lines of evidence highlight the importance of both ATG9, which brings key proteins to the nascent autophagosome, and phosphoinositides, in particular PI4P, in different steps of autophagy. PI4P is indeed detected on early‐stage autophagosomes, omegasomes, and phagophores and is crucial in the formation of autophagosomes and the completion of autophagy flux .…”

Section: Golgi Complex Roles In Autophagosome Biogenesis and Maturationmentioning

confidence: 99%

Hijacking intracellular membranes to feed autophagosomal growth

Staiano

Zappa

2019

FEBS Letters

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Autophagy is widely considered as a housekeeping mechanism that enables cells to survive stress conditions and, in particular, nutrient deprivation. Autophagy begins with the formation of the phagophore that expands and closes around cytosolic material and damaged organelles destined for degradation. The execution of this complex machinery is guaranteed by the coordinated action of more than 40 ATG (autophagy‐related) proteins that control the entire process at different stages from the biogenesis of the autophagosome to cargo sequestration and fusion with lysosomes. Autophagosome biogenesis occurs at multiple intracellular sites, such as the endoplasmic reticulum (ER) and the plasma membrane. Soon after the formation of the phagophore, the nascent autophagosome progressively grows in size and ultimately closes by recruiting intracellular membranes. In this review, we focus on the contribution of three membrane sources – the ER, the ER–Golgi intermediate compartment, and the Golgi complex – to autophagosome biogenesis and expansion. We also highlight the interplay between the secretory pathway and autophagy in cells when nutrients are scarce.

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“…Arfaptin-2, in complex with ARL1, ARF1 and PKD2, selectively regulates the secretion of MMP2 and MMP7 [80], thus confirming a role for PI4P in Golgi export of selected cargos. A recent study by Judith et al [81] defined a role for Arfaptin-2 in the redistribution of the autophagy protein ATG9 from the TGN, where it is localized in control fed conditions, to the ATG9-positive compartments formed under starvation, a step required for autophagy initiation, thus expanding the role of PI4P and its effectors in the Golgi export of cargoes not destined for secretion. Because PI4P is regulated at the level of MCSs, one logical consequence of contact site modulation would be an alteration in cargo trafficking and secretion.…”

Section: Interplay Between Er-tgn Contact Sites the Pi4p Pool And Gomentioning

confidence: 99%

Illuminating the membrane contact sites between the endoplasmic reticulum and the trans‐Golgi network

2019

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Membrane contact sites (MCSs) between different organelles have been identified and extensively studied over the last decade. Several classes of MCSs have now well‐established roles, although the contacts between the endoplasmic reticulum (ER) and the trans‐side of the Golgi network (TGN) have long remained elusive. Until recently, the study of ER–TGN contact sites has represented a major challenge in the field, as a result of the lack of suitable visualization and isolation techniques. Only in the last 5 years has the combination of advanced technologies and innovative approaches permitted the identification of new molecular players and the functions of ER–TGN MCSs that couple lipid metabolism and anterograde transport. Although much has yet to be discovered, it is now established that ER–TGN MCSs control phosphatidyl‐4‐phosphate homeostasis by coupling the cis and the trans activity of the ER‐resident 4‐phosphatase Sac1. In this review, we focus on recent advances on the composition and function of ER–TGN MCSs.

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ATG9A shapes the forming autophagosome through Arfaptin 2 and phosphatidylinositol 4-kinase IIIβ

Cited by 171 publications

References 55 publications

Determining the content of vesicles captured by golgin tethers using LOPIT-DC

Determining the content of vesicles captured by golgin tethers using LOPIT-DC

Hijacking intracellular membranes to feed autophagosomal growth

Illuminating the membrane contact sites between the endoplasmic reticulum and the trans‐Golgi network

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