Regulation of Golgi Cisternal Progression by Ypt/Rab GTPases

Kim, Jane J.; Lipatova, Zhanna; Majumdar, Uddalak; Segev, Nava

doi:10.1016/j.devcel.2016.01.016

Cited by 38 publications

(48 citation statements)

References 39 publications

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“…As yeast Golgi compartments undergo cisternal maturation (Losev et al, 2006), we expect a GEF to arrive at the Golgi coincident with or slightly before its substrate. In agreement with previous studies, we found that wild-type mNG-Ypt32 accumulated at the TGN after Sec7, correlating with activation by TRAPPII (Figure 4C and 5D; Kim et al, 2016; McDonold and Fromme, 2014; Thomas and Fromme, 2016). In contrast, mNG-Ypt32 HVD1 arrived at the Golgi before Sec7, coinciding with peak TRAPPIII recruitment (Thomas et al, 2018), suggesting that TRAPPIII weakly activates Ypt32 HVD1 in cells.…”

Section: Resultssupporting

confidence: 93%

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A Steric Gating Mechanism Dictates the Substrate Specificity of a Rab-GEF

2019

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Summary Correct localization of Rab GTPases in cells is critical for proper function in membrane trafficking, yet the mechanisms that target Rabs to specific subcellular compartments remain controversial. Guanine nucleotide exchange factors (GEFs) activate and consequently stabilize Rab substrates on membranes, thus implicating GEFs as the primary determinants of Rab localization. A competing hypothesis is that the Rab C-terminal hypervariable domain (HVD) serves as a subcellular targeting signal. In this study we present a unifying mechanism in which the HVD controls targeting of certain Rabs by mediating interaction with their GEFs. We demonstrate that the TRAPP complexes, two related GEFs that use the same catalytic site to activate distinct Rabs, distinguish between Ypt1 (Rab1) and Ypt31/32 (Rab11) via their divergent HVDs. Remarkably, we find that HVD length gates Rab access to the TRAPPII complex by constraining the distance between the nucleotide-binding domain and the membrane surface.

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Section: Resultssupporting

confidence: 93%

“…In wild-type cells, mNG-Ypt1 localizes to the Golgi, overlapping significantly with Sec7 (Figure 5B; Kim et al, 2016; Sclafani et al, 2010). Consistent with its ability to support cell viability, mNG-Ypt1 HVD32 was largely activated at Sec7-labeled late-Golgi compartments.…”

Section: Resultsmentioning

confidence: 96%

A Steric Gating Mechanism Dictates the Substrate Specificity of a Rab-GEF

2019

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“…Titration of activated Ypt31 caused up to 2.5‐fold increase in the rate of maturation of transitional to late cisterna (from 10 to 4 s), and a fivefold increase in the accumulation of the trans‐Golgi vesicles compared to those of the wild type, while inactivation of Ypt31 had the opposite effect. These effects were specific for each Ypt . These results implicate Ypt1 in regulation of early to transitional and Ypt31 in transitional to late Golgi progression.…”

Section: The Golgi Ypt/rabsmentioning

confidence: 63%

“…When the Ypts were co‐localized with those Golgi cisternal markers, live‐cell and IF approaches gave the same answer—Ypt1 and Ypt31 reside on the opposite sides of the Golgi apparatus, with Ypt1 mostly on the early Golgi and Ypt31 on late Golgi. In addition, ~ 20% of Ypt1 and Ypt31 also localize to the transitional cisterna, where they co‐localize with early and late Golgi markers and with each other . Thus, functional and rigorous localization analyses agree that Ypt1 resides and functions in the early Golgi whereas Ypt31 functions and localizes at the late Golgi.…”

Section: The Golgi Ypt/rabsmentioning

confidence: 79%

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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“…Third, the endocytic collar that just precedes the hyphal tip is a uniquely fungal structure that is important for the maintenance of somatic fungal growth, and little is known about endocytic protein dynamics there (Araujo‐Bazán et al ., ; Lee et al ., ; Taheri‐Talesh et al ., ; Upadhyay and Shaw, ; Delgado‐Álvarez et al ., ; Echauri‐Espinosa et al ., ; Schultzhaus and Shaw, ; Schultzhaus et al ., ). Finally, membrane progression through Golgi is coupled to polarized growth and is easily visualized in filamentous fungi, allowing for the examination of any clathrin structures that might be found at this organelle (Bracker, ; Howard, ; Dargent et al ., ; Cole et al ., ; Hohmann‐Marriott et al ., ; Bowman et al ., ; Pantazopoulou and Peñalva, ; Harris, ; Pinar et al ., ; Pantazopoulou et al ., ; Sánchez‐León et al ., ; Kim et al ., ; Pantazopoulou, ; Riquelme et al ., ).…”

Section: Introductionmentioning

confidence: 99%

Clathrin localization and dynamics in Aspergillus nidulans

Schultzhaus

Johnson

Shaw

2016

Molecular Microbiology

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Cell growth necessitates extensive membrane remodeling events including vesicle fusion or fission, processes that are regulated by coat proteins. The hyphal cells of filamentous fungi concentrate both exocytosis and endocytosis at the apex. This investigation focuses on clathrin in Aspergillus nidulans, with the aim of understanding its role in membrane remodeling in growing hyphae. We examined clathrin heavy chain (ClaH-GFP) which localized to three distinct subcellular structures: late Golgi (trans-Golgi equivalents of filamentous fungi), which are concentrated just behind the hyphal tip but are intermittently present throughout all hyphal cells; the region of concentrated endocytosis just behind the hyphal apex (the "endocytic collar"); and small, rapidly moving puncta that were seen trafficking long distances in nearly all hyphal compartments. ClaH localized to distinct domains on late Golgi, and these clathrin "hubs" dispersed in synchrony after the late Golgi marker PH . Although clathrin was essential for growth, ClaH did not colocalize well with the endocytic patch marker fimbrin. Tests of FM4-64 internalization and repression of ClaH corroborated the observation that clathrin does not play an important role in endocytosis in A. nidulans. A minor portion of ClaH puncta exhibited bidirectional movement, likely along microtubules, but were generally distinct from early endosomes.

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Regulation of Golgi Cisternal Progression by Ypt/Rab GTPases

Cited by 38 publications

References 39 publications

A Steric Gating Mechanism Dictates the Substrate Specificity of a Rab-GEF

A Steric Gating Mechanism Dictates the Substrate Specificity of a Rab-GEF

Ypt/Rab GTPases and their TRAPP GEFs at the Golgi

Clathrin localization and dynamics in Aspergillus nidulans

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