TRAPPopathies: An emerging set of disorders linked to variations in the genes encoding transport protein particle (TRAPP)‐associated proteins

Sacher, Michael; Shahrzad, Nassim; Kamel, Hiba; Milev, Miroslav P.

doi:10.1111/tra.12615

Cited by 78 publications

(112 citation statements)

References 224 publications

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“…Mutations in TRAPPC11 have been linked to disease . The phenotypes are broad and include liver and eye involvement, achalasia, alacrima and intellectual deficit.…”

Section: Discussionmentioning

confidence: 99%

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

Stanga

Zhao

Milev

et al. 2019

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TRAPPC11 has been implicated in membrane traffic and lipid‐linked oligosaccharide synthesis, and mutations in TRAPPC11 result in neuromuscular and developmental phenotypes. Here, we show that TRAPPC11 has a role upstream of autophagosome formation during macroautophagy. Upon TRAPPC11 depletion, LC3‐positive membranes accumulate prior to, and fail to be cleared during, starvation. A proximity biotinylation assay identified ATG2B and its binding partner WIPI4/WDR45 as TRAPPC11 interactors. TRAPPC11 depletion phenocopies that of ATG2 and WIPI4 and recruitment of both proteins to membranes is defective upon reduction of TRAPPC11. We find that a portion of TRAPPC11 and other TRAPP III proteins localize to isolation membranes. Fibroblasts from a patient with TRAPPC11 mutations failed to recruit ATG2B‐WIPI4, suggesting that this interaction is physiologically relevant. Since ATG2B‐WIPI4 is required for isolation membrane expansion, our study suggests that TRAPPC11 plays a role in this process. We propose a model whereby the TRAPP III complex participates in the formation and expansion of the isolation membrane at several steps.

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“…Mutations in TRAPPC11 have been linked to disease . The phenotypes are broad and include liver and eye involvement, achalasia, alacrima and intellectual deficit.…”

Section: Discussionmentioning

confidence: 99%

“…Mutations in TRAPPC11 have been linked to disease. 61 The phenotypes are broad and include liver and eye involvement, achalasia, alacrima and intellectual deficit. However, virtually all individuals with TRAPPC11 mutations display some form of muscular pathology or an elevated creatine kinase level.…”

Section: Discussionmentioning

confidence: 99%

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

Stanga

Zhao

Milev

et al. 2019

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“…Roles for TRAPP II and III complexes in secretion and for TRAPP III in autophagy were suggested . However, as in yeast, we question whether the fact that TRAPP I complex was not observed in mammalian cell lysates is due to the tendency of TRAPP complexes to aggregate.…”

Section: Trapp Gefs At the Golgimentioning

confidence: 94%

Ypt/Rab GTPases and their TRAPP GEFs at the Golgi

Lipatova

Segev

2019

FEBS Letters

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The conserved Ypt/Rab GTPases regulate the different steps of all intracellular trafficking pathways. Ypt/Rabs are activated by their specific nucleotide exchangers termed GEFs, and when GTP bound, they recruit their downstream effectors, which mediate vesicular transport substeps. In the yeast exocytic pathway, Ypt1 and Ypt31/32 regulate traffic through the Golgi and the conserved modular TRAPP complex acts a GEF for both Ypt1 and Ypt31/32. However, the precise localization and function of these Ypts have been under debate, as is the identity of their corresponding GEFs. We have established that Ypt1 and Ypt31 reside on the two sides of the Golgi, early and late, respectively, and regulate Golgi cisternal progression. We and others have shown that whereas a single TRAPP complex, TRAPP II, activates Ypt31, three TRAPP complexes can activate Ypt1: TRAPPs I, III, and IV. We propose that TRAPP I and II activate Ypt1 and Ypt31, respectively, at the Golgi, whereas TRAPP III and IV activate Ypt1 in autophagy. Resolving these issues is important because both Rabs and TRAPPs are implicated in multiple human diseases, ranging from cancer to neurodegenerative diseases.

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“…In yeast, mutations in TRAPPs are typically lethal or cause strongly impaired growth (Kim et al, 2016). In humans, mutations in TRAPP components have been implicated in a variety of diseases (Milev et al, 2015; Sacher et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…In yeast, TRAPPII functions in late Golgi and TRAPPIII in early Golgi and autophagy (Kim et al, 2016; Riedel et al, 2018; Thomas et al, 2018). In metazoans, TRAPPII is involved in membrane traffic in the biosynthetic pathway, and TRAPPIII functions in autophagosome formation and autophagy (Yamasaki et al, 2009; Scrivens et al, 2011; Bassik et al, 2013; Lamb et al, 2016; Ramirez-Peinado et al, 2017; Sacher et al, 2018). Furthermore, TRAPP complexes have been shown to function as Guanine nucleotide Exchange Factors (GEF) for Rab GTPases in both yeast and metazoans (Jenkins et al, 2018; Riedel et al, 2018; Thomas et al, 2018; Thomas et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Proteomic studies of the Arabidopsis TRAPP complexes reveal conserved organization and a novel plant-specific component with a role in plant development

Garcia

Ravikumar

et al. 2019

Preprint

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2How the membrane trafficking system spatially organizes intracellular activities and 3 3 intercellular signaling networks is not well understood in plants. The Transport Protein 3 4Particle (TRAPP) complexes are known to play key roles in selective delivery of 3 5 membrane vesicles to various subcellular compartments in yeast and animals, but 3 6 remain to be fully characterized in plants. Here we interrogate the TRAPP complexes in 3 7 Arabidopsis using quantitative proteomic approaches. TRS33 is a component shared by 3 8 all TRAPP complexes in yeast and animals, and the Arabidopsis AtTRS33 is essential 3 9for the subcellular dynamics of other TRAPP components. Affinity purification of 4 0AtTRS33 followed by quantitative mass spectrometry identified fourteen interacting 4 1 proteins; these include not only thirteen homologs of all known TRAPP components in 4 2 yeast and mammals but also a novel protein we named TRAPP-interacting plant protein 4 3 (TRIPP), which is conserved in multi-cellular photosynthetic organisms. Proteomic and 4 4 molecular analyses showed that TRIPP specifically associates with the TRAPPII 4 5 complex in vivo and directly interacts with the TRAPPII-specific subunits but not the 4 6 subunits shared with TRAPPIII. TRIPP co-localizes with a subset of TRS33 4 7

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TRAPPopathies: An emerging set of disorders linked to variations in the genes encoding transport protein particle (TRAPP)‐associated proteins

Cited by 78 publications

References 224 publications

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

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

Ypt/Rab GTPases and their TRAPP GEFs at the Golgi

Proteomic studies of the Arabidopsis TRAPP complexes reveal conserved organization and a novel plant-specific component with a role in plant development

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