TRAPPC11 functions in autophagy by recruiting ATG2B‐WIPI4/WDR45 to preautophagosomal membranes

Stanga, Daniela; Zhao, Qingchuan; Milev, Miroslav P.; Saint‐Dic, Djenann; Jiménez-Mallebrera, C.; Sacher, Michael

doi:10.1111/tra.12640

Cited by 56 publications

(57 citation statements)

References 79 publications

(212 reference statements)

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“…Recent work has shown that the ESCRT‐III component CHMP2A regulates the separation of inner and outer phagophore membranes , and more recently, VPS37A is essential for phagophore closure . In addition to the ESCRT‐III machinery, TRAPPC11, a member of TRAPP complexes involved in membrane trafficking, has been shown to recruit ATG2B‐WIPI4 to phagophores in an ATG9A‐dependent manner . The depletion of TRAPC11 results in a phenotype similar to that of ATG2A/B DKO and ATG2A‐mLIR .…”

Section: Resultsmentioning

confidence: 99%

A conserved ATG2‐GABARAP family interaction is critical for phagophore formation

et al. 2020

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The intracellular trafficking pathway, macroautophagy, is a recycling and disposal service that can be upregulated during periods of stress to maintain cellular homeostasis. An essential phase is the elongation and closure of the phagophore to seal and isolate unwanted cargo prior to lysosomal degradation. Human ATG2A and ATG2B proteins, through their interaction with WIPI proteins, are thought to be key players during phagophore elongation and closure, but little mechanistic detail is known about their function. We have identified a highly conserved motif driving the interaction between human ATG2 and GABARAP proteins that is in close proximity to the ATG2‐WIPI4 interaction site. We show that the ATG2A‐GABARAP interaction mutants are unable to form and close phagophores resulting in blocked autophagy, similar to ATG2A/ATG2B double‐knockout cells. In contrast, the ATG2A‐WIPI4 interaction mutant fully restored phagophore formation and autophagy flux, similar to wild‐type ATG2A. Taken together, we provide new mechanistic insights into the requirements for ATG2 function at the phagophore and suggest that an ATG2‐GABARAP/GABARAP‐L1 interaction is essential for phagophore formation, whereas ATG2‐WIPI4 interaction is dispensable.

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Section: Resultsmentioning

confidence: 99%

A conserved ATG2‐GABARAP family interaction is critical for phagophore formation

et al. 2020

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“…The wide range of TRAPPopathies associated with the human TRAPC11 mutations include, among others, muscular dystrophy, myopathy, and liver disease (Sacher et al, 2019) and point toward yet-undiscovered functions of the AtTRAPPC11/ROG2 in plant physiology. The role of human TRAPPC11 upstream of autophagosome formation was recently demonstrated (Stanga et al, 2019); a similar function warrants exploration in plant cells, especially under biotic and abiotic stress.…”

Section: Loss Of Attrappc11 Affects Root Growth and Plant Stress Respmentioning

confidence: 85%

AtTRAPPC11/ROG2: A Role for TRAPPs in Maintenance of the Plant Trans-Golgi Network/Early Endosome Organization and Function

et al. 2019

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The dynamic trans-Golgi network/early endosome (TGN/EE) facilitates cargo sorting and trafficking and plays a vital role in plant development and environmental response. Transport protein particles (TRAPPs) are multi-protein complexes acting as guanine nucleotide exchange factors and possibly as tethers, regulating intracellular trafficking. TRAPPs are essential in all eukaryotic cells and are implicated in a number of human diseases. It has been proposed that they also play crucial roles in plants; however, our current knowledge about the structure and function of plant TRAPPs is very limited. Here, we identified and characterized AtTRAPPC11/RESPONSE TO OLIGOGALACTURONIDE2 (AtTRAPPC11/ROG2), a TGN/EE-associated, evolutionarily conserved TRAPP protein in Arabidopsis (Arabidopsis thaliana). AtTRAPPC11/ROG2 regulates TGN integrity, as evidenced by altered TGN/EE association of several residents, including SYNTAXIN OF PLANTS61, and altered vesicle morphology in attrappc11/rog2 mutants. Furthermore, endocytic traffic and brefeldin A body formation are perturbed in attrappc11/rog2, suggesting a role for AtTRAPPC11/ROG2 in regulation of endosomal function. Proteomic analysis showed that AtTRAPPC11/ROG2 defines a hitherto uncharacterized TRAPPIII complex in plants. In addition, attrappc11/rog2 mutants are hypersensitive to salinity, indicating an undescribed role of TRAPPs in stress responses. Overall, our study illustrates the plasticity of the endomembrane system through TRAPP protein functions and opens new avenues to explore this dynamic network.

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“…Purification with Trs120-S showed that in addition to the 'core TRAPP hetero-heptamer' and the TRAPPII-specific subunits Trs120, Trs130 and Trs65, TRAPPII contains Tca17 ( Fig 1D and 1E), which was missing in the single particle EM yeast TRAPPII structure [30], but is a demonstrated yeast TRAPPII component [8,9]. The finding that TRAPPC11, TRAPPC12 and TRAPPC13 are absent from TRAPPII suggested that they belong to TRAPPIII, as in mammalian TRAPPs) [31][32][33][34], which is confirmed below. Thus, A. nidulans TRAPPs resemble those of metazoans to a greater extent than those of S. cerevisiae.…”

Section: Composition Of a Nidulans Trappsmentioning

confidence: 99%

Characterization of Aspergillus nidulans TRAPPs uncovers unprecedented similarities between fungi and metazoans and reveals the modular assembly of TRAPPII

et al. 2019

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TRAnsport Protein Particle complexes (TRAPPs) are ubiquitous regulators of membrane traffic mediating nucleotide exchange on the Golgi regulatory GTPases RAB1 and RAB11. In S. cerevisiae and metazoans TRAPPs consist of two large oligomeric complexes: RAB11-activating TRAPPII and RAB1-activating TRAPPIII. These share a common core TRAPPI heteroheptamer, absent in metazoans but detected in minor proportions in yeast, likely originating from in vitro-destabilized TRAPPII/III. Despite overall TRAPP conservation, the budding yeast genome has undergone extensive loss of genes, and lacks homologues of some metazoan TRAPP subunits. With nearly twice the total number of genes of S. cerevisiae, another ascomycete Aspergillus nidulans has also been used for studies on TRAPPs. We combined sizefractionation chromatography with single-step purification coupled to mass-spectrometry and negative-stain electron microscopy to establish the relative abundance, composition and architecture of Aspergillus TRAPPs, which consist of TRAPPII and TRAPPIII in a 2:1 proportion, plus a minor amount of TRAPPI. We show that Aspergillus TRAPPIII contains homologues of metazoan TRAPPC11, TRAPPC12 and TRAPPC13 subunits, absent in S. cerevisiae, and establish that these subunits are recruited to the complex by Tca17/TRAPPC2L, which itself binds to the 'Trs33 side' of the complex. Thus Aspergillus TRAPPs compositionally resemble mammalian TRAPPs to a greater extent than those in budding yeast. Exploiting the ability of constitutively-active (GEF-independent, due to accelerated GDP release) RAB1* and RAB11* alleles to rescue viability of null mutants lacking essential TRAPP subunits, we establish that the only essential role of TRAPPs is activating RAB1 and RAB11, and genetically classify each essential subunit according to their role(s) in TRAPPII (TRAPPII-specific subunits) or TRAPPII and TRAPPIII (core TRAPP subunits). Constitutively-active RAB mutant combinations allowed examination of TRAPP composition in mutants lacking essential subunits, which led to the discovery of a stable Trs120/Trs130/Trs65/Tca17 TRAPPII-specific subcomplex whose Trs20-and Trs33-dependent assembly onto core TRAPP generates TRAPPII.

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TRAPPC11 functions in autophagy by recruiting ATG2B‐WIPI4/WDR45 to preautophagosomal membranes

Cited by 56 publications

References 79 publications

A conserved ATG2‐GABARAP family interaction is critical for phagophore formation

A conserved ATG2‐GABARAP family interaction is critical for phagophore formation

AtTRAPPC11/ROG2: A Role for TRAPPs in Maintenance of the Plant Trans-Golgi Network/Early Endosome Organization and Function

Characterization of Aspergillus nidulans TRAPPs uncovers unprecedented similarities between fungi and metazoans and reveals the modular assembly of TRAPPII

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