A systematic approach to identify recycling endocytic cargo depending on the GARP complex

Eising, Sebastian; Thiele, Lisa; Fröhlich, Florian

doi:10.7554/elife.42837

Cited by 36 publications

(31 citation statements)

References 59 publications

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“…Insulin stimulation mobilizes GSVs to fuse with the PM, but in its continuous presence, GLUT4 molecules are internalized and recycled back to the PM in endosomal vesicles that are distinct from GSVs. Recycling of fungal nutrient transporters has also been reported when growth conditions change ( [76,[80][81][82] and references therein).…”

Section: Endocytosis Of Apical Cargoes and Transporters Occurs By Dismentioning

confidence: 95%

Life and Death of Fungal Transporters under the Challenge of Polarity

Dimou

Diallinas

2020

IJMS

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Eukaryotic plasma membrane (PM) transporters face critical challenges that are not widely present in prokaryotes. The two most important issues are proper subcellular traffic and targeting to the PM, and regulated endocytosis in response to physiological, developmental, or stress signals. Sorting of transporters from their site of synthesis, the endoplasmic reticulum (ER), to the PM has been long thought, but not formally shown, to occur via the conventional Golgi-dependent vesicular secretory pathway. Endocytosis of specific eukaryotic transporters has been studied more systematically and shown to involve ubiquitination, internalization, and sorting to early endosomes, followed by turnover in the multivesicular bodies (MVB)/lysosomes/vacuole system. In specific cases, internalized transporters have been shown to recycle back to the PM. However, the mechanisms of transporter forward trafficking and turnover have been overturned recently through systematic work in the model fungus Aspergillus nidulans. In this review, we present evidence that shows that transporter traffic to the PM takes place through Golgi bypass and transporter endocytosis operates via a mechanism that is distinct from that of recycling membrane cargoes essential for fungal growth. We discuss these findings in relation to adaptation to challenges imposed by cell polarity in fungi as well as in other eukaryotes and provide a rationale of why transporters and possibly other housekeeping membrane proteins ‘avoid’ routes of polar trafficking.

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Section: Endocytosis Of Apical Cargoes and Transporters Occurs By Dismentioning

confidence: 95%

Life and Death of Fungal Transporters under the Challenge of Polarity

Dimou

Diallinas

2020

IJMS

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“…HPLC analysis was performed on a C30 reversephase column (Thermo Acclaim C30, 2.1 × 250 mm, 3 μm, operated at 50˚C; Thermo Fisher Scientific) connected to an HP 1100 series HPLC (Agilent) HPLC system and a QEx-activePLUS Orbitrap mass spectrometer (Thermo Fisher Scientific) equipped with a heated electrospray ionization (HESI) probe. The analysis was performed as described previously [70]. Peaks were analyzed using the Lipid Search algorithm (MKI, Tokyo, Japan).…”

Section: Plos Geneticsmentioning

confidence: 99%

Uptake of exogenous serine is important to maintain sphingolipid homeostasis in Saccharomyces cerevisiae

et al. 2020

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Sphingolipids are abundant and essential molecules in eukaryotes that have crucial functions as signaling molecules and as membrane components. Sphingolipid biosynthesis starts in the endoplasmic reticulum with the condensation of serine and palmitoyl-CoA. Sphingolipid biosynthesis is highly regulated to maintain sphingolipid homeostasis. Even though, serine is an essential component of the sphingolipid biosynthesis pathway, its role in maintaining sphingolipid homeostasis has not been precisely studied. Here we show that serine uptake is an important factor for the regulation of sphingolipid biosynthesis in Saccharomyces cerevisiae. Using genetic experiments, we find the broad-specificity amino acid permease Gnp1 to be important for serine uptake. We confirm these results with serine uptake assays in gnp1Δ cells. We further show that uptake of exogenous serine by Gnp1 is important to maintain cellular serine levels and observe a specific connection between serine uptake and the first step of sphingolipid biosynthesis. Using mass spectrometry-based flux analysis, we further observed imported serine as the main source for de novo sphingolipid biosynthesis. Our results demonstrate that yeast cells preferentially use the uptake of exogenous serine to regulate sphingolipid biosynthesis. Our study can also be a starting point to analyze the role of serine uptake in mammalian sphingolipid metabolism.

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“…After endocytosis, the cargos recycle back to the tip via the Golgi and the SPK (Hernández-González et al 2018;Casler et al 2019), and results suggest, in both S. cerevisiae and A. nidulans, that this recycling is mediated by the Golgi-Associated Retrograde Protein (GARP) complex. In detail, it was recently shown that Dnf1 and Dnf2 (orthologues of DnfA and DnfB) are substrates of the GARP complex and recycle back to the PM, while their endocytosis requires the AP-2 complex (Eising, Thiele and Fröhlich 2019). Interestingly, the GARP complex also contributes to the recycling of SLs (Fröhlich et al 2015), and consistently SLs are known to be required for polarity maintenance (Cheng et al 2002;Pearson et al 2004;Li et al 2006), probably by promoting the localization of the AP-2 complex in the subapical collar of the hyphae (Fernandes et al 2016;Martzoukou et al 2017).…”

Section: Organization Of Apical Regionsmentioning

confidence: 99%

Fungal plasma membrane domains

Αθανασόπουλος

André

Sophianopoulou

et al. 2019

FEMS Microbiology Reviews

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The plasma membrane (PM) performs a plethora of physiological processes, the coordination of which requires spatial and temporal organization into specialized domains of different sizes, stability, protein/lipid composition and overall architecture. Compartmentalization of the PM has been particularly well studied in the yeast Saccharomyces cerevisiae, where five non-overlapping domains have been described: The Membrane Compartments containing the arginine permease Can1 (MCC), the H+-ATPase Pma1 (MCP), the TORC2 kinase (MCT), the sterol transporters Ltc3/4 (MCL), and the cell wall stress mechanosensor Wsc1 (MCW). Additional cortical foci at the fungal PM are the sites where clathrin-dependent endocytosis occurs, the sites where the external pH sensing complex PAL/Rim localizes, and sterol-rich domains found in apically grown regions of fungal membranes. In this review, we summarize knowledge from several fungal species regarding the organization of the lateral PM segregation. We discuss the mechanisms of formation of these domains, and the mechanisms of partitioning of proteins there. Finally, we discuss the physiological roles of the best-known membrane compartments, including the regulation of membrane and cell wall homeostasis, apical growth of fungal cells and the newly emerging role of MCCs as starvation-protective membrane domains.

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A systematic approach to identify recycling endocytic cargo depending on the GARP complex

Cited by 36 publications

References 59 publications

Life and Death of Fungal Transporters under the Challenge of Polarity

Life and Death of Fungal Transporters under the Challenge of Polarity

Uptake of exogenous serine is important to maintain sphingolipid homeostasis in Saccharomyces cerevisiae

Fungal plasma membrane domains

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