Gyp1 has a dual function as Ypt1 GAP and interaction partner of Atg8 in selective autophagy

Mitter, Anne Lisa; Schlotterhose, Petra; Krick, Roswitha

doi:10.1080/15548627.2019.1569929

Cited by 9 publications

(9 citation statements)

References 91 publications

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“…Gyp1 has dual functions, as a GAP for Ypt1 and as an interacting partner of Atg8 in selective autophagy ( Mitter et al, 2019 ). For its stability and normal subcellular localization, Gyp1 (a GAP for Ypt1) needs to interact with Ypt32 ( Rivera-Molina and Novick, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

The GTPase-Activating Protein FgGyp1 Is Important for Vegetative Growth, Conidiation, and Virulence and Negatively Regulates DON Biosynthesis in Fusarium graminearum

Zheng

Yuan

et al. 2021

Front. Microbiol.

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Ypt1 is a small Rab GTPase in yeast, Gyp1 functions at the Golgi as a negative regulator of Ypt1. Gyp1 homologs are conserved in filamentous fungi. However, the roles of Gyp1 in phytopathogenic fungi are still unclear. Herein, we investigated the functions of FgGyp1 in the wheat pathogen Fusarium graminearum by live-cell imaging, genetic, and pathological analyses. Targeted gene replacement method was used to delete FgGYP1 in F. graminearum. Phenotypic analyses showed that FgGyp1 is critically important not only for the vegetative growth of F. graminearum but also its conidiation. The mutant’s vegetative growth was significantly reduced by 70% compared to the wild type PH-1. The virulence of FgGYP1 deletion mutant was significantly decreased when compared with the wild type PH-1. We further found that FgGyp1 negatively regulates DON production of the fungus. Live-cell imaging clearly demonstrated that FgGyp1 mainly localizes to the Golgi apparatus. Moreover, the TBC domain, C-terminal, and N-terminal regions of FgGyp1 are found to be indispensable for its biological functions and normal localization. The Arg357 residue of FgGyp1 is essential for its functions but dispensable for the normal localization of the protein, while the Arg284 residue is not required for both the functions and normal localization of the protein. Furthermore, we showed that FgGyp1 essentially hydrolyzes the GTP-bound FgRab1 (activated form) to its corresponding GDP-bound (inactive) form in vitro, suggesting that FgGyp1 is a GTPase-activating protein (GAP) for FgRab1. Finally, FgGyp1 was found to be important for FgSnc1-mediated fusion of secretory vesicles from the Golgi with the plasma membrane in F. graminearum. Put together, these data demonstrate that FgGyp1 functions as a GAP for FgRab1 and is important for vegetative growth, conidiation and virulence, and negatively regulates DON biosynthesis in F. graminearum.

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Section: Discussionmentioning

confidence: 99%

The GTPase-Activating Protein FgGyp1 Is Important for Vegetative Growth, Conidiation, and Virulence and Negatively Regulates DON Biosynthesis in Fusarium graminearum

Zheng

Yuan

et al. 2021

Front. Microbiol.

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“…Moreover, a recent study suggests that Gyp1, a GAP (GTPase-activating protein) of Ypt1, has been identified as a novel Atg8 interaction partner. Loss of Gyp1, its GAP activity, or its first AIM; AIM1 (160-163 a.a.) causes a partial reduction in mitophagy, yet how Gyp1 contributes to autophagosome formation remains elusive [31].…”

Section: Pink1-mediated Ubiquitin Phosphorylationmentioning

confidence: 99%

Mitochondrial clearance: mechanisms and roles in cellular fitness

Onishi

Okamoto

2021

FEBS Letters

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Edited by Agnieszka ChacinskaMitophagy is one of the selective autophagy pathways that catabolizes dysfunctional or superfluous mitochondria. Under mitophagy-inducing conditions, mitochondria are labeled with specific molecular landmarks that recruit the autophagy machinery to the surface of mitochondria, enclosed into autophagosomes, and delivered to lysosomes (vacuoles in yeast) for degradation. As damaged mitochondria are the major sources of reactive oxygen species, mitophagy is critical for mitochondrial quality control and cellular health. Moreover, appropriate control of mitochondrial quantity via mitophagy is vital for the energy supply-demand balance in cells and whole organisms, cell differentiation, and developmental programs. Thus, it seems conceivable that defects in mitophagy could elicit pleiotropic pathologies such as excess inflammation, tissue injury, neurodegeneration, and aging. In this review, we will focus on the molecular basis and physiological relevance of mitophagy, and potential of mitophagy as a therapeutic target to overcome such disorders.

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“…Gyp1 also plays a role in autophagy. It regulates the disassembly of Ytp1–Atg1 complexes, as well as the interaction of cargo receptor and Atg8 proteins in selective autophagy [ 93 ]. In humans, 38 Rab GAPs have been identified, with TBC1D20 (Gyp8 in yeast) being the specific (but not exclusive) GAP for Rab1.…”

Section: Rab1mentioning

confidence: 99%

Focus on the Small GTPase Rab1: A Key Player in the Pathogenesis of Parkinson’s Disease

Martı́nez-Menárguez

Martínez‐Alonso

Cara-Esteban

et al. 2021

IJMS

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Parkinson’s disease (PD) is the second most frequent neurodegenerative disease. It is characterized by the loss of dopaminergic neurons in the substantia nigra and the formation of large aggregates in the survival neurons called Lewy bodies, which mainly contain α-synuclein (α-syn). The cause of cell death is not known but could be due to mitochondrial dysfunction, protein homeostasis failure, and alterations in the secretory/endolysosomal/autophagic pathways. Survival nigral neurons overexpress the small GTPase Rab1. This protein is considered a housekeeping Rab that is necessary to support the secretory pathway, the maintenance of the Golgi complex structure, and the regulation of macroautophagy from yeast to humans. It is also involved in signaling, carcinogenesis, and infection for some pathogens. It has been shown that it is directly linked to the pathogenesis of PD and other neurodegenerative diseases. It has a protective effect against α–σψν toxicity and has recently been shown to be a substrate of LRRK2, which is the most common cause of familial PD and the risk of sporadic disease. In this review, we analyze the key aspects of Rab1 function in dopamine neurons and its implications in PD neurodegeneration/restauration. The results of the current and former research support the notion that this GTPase is a good candidate for therapeutic strategies.

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Gyp1 has a dual function as Ypt1 GAP and interaction partner of Atg8 in selective autophagy

Cited by 9 publications

References 91 publications

The GTPase-Activating Protein FgGyp1 Is Important for Vegetative Growth, Conidiation, and Virulence and Negatively Regulates DON Biosynthesis in Fusarium graminearum

The GTPase-Activating Protein FgGyp1 Is Important for Vegetative Growth, Conidiation, and Virulence and Negatively Regulates DON Biosynthesis in Fusarium graminearum

Mitochondrial clearance: mechanisms and roles in cellular fitness

Focus on the Small GTPase Rab1: A Key Player in the Pathogenesis of Parkinson’s Disease

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