ARF GTPases and Their Ubiquitous Role in Intracellular Trafficking Beyond the Golgi

Adarska, Petia; Wong-Dilworth, Luis; Bottanelli, Francesca

doi:10.3389/fcell.2021.679046

Cited by 55 publications

(51 citation statements)

References 73 publications

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“…Elegant in vitro studies have shown that a VAPA-OSBP complex is sufficient to transfer cholesterol and PtdIns(4) P in vitro between vesicles (de la Mora et al, 2021). In living cells, this process in addition requires ARF1 that, by cycling between its GDP and GTP-bound forms, contributes to the recruitment of OSBP at the ER-Golgi MCSs (Adarska et al, 2021; Donaldson et al, 2005; Nakatsu & Kawasaki, 2021). The mechanism that ensures initial recruitment of ARF1 at MCSs is not known.…”

Section: Discussionmentioning

confidence: 99%

Anthrax intoxication reveals that ER-Golgi membrane contact sites control the formation of plasma membrane lipid nanodomains

Anwar

Sergeeva

Abrami

et al. 2022

Preprint

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To promote infections, pathogens exploit host cell machineries including structural elements of the plasma membrane. Studying these interactions and identifying involved molecular players is an ideal way to gain insights into the fundamental biology of the host cell. Here, using the anthrax toxin, we screened a 1500-gene library of regulatory, cell surface, and membrane trafficking genes for their involvement in the intoxication process. We found that the ER-Golgi localized proteins TMED2 and TMED10 are required for toxin oligomerization at the cell surface, an essential step for anthrax intoxication that depends on localization to cholesterol-rich lipid nanodomains. Further biochemical, morphological and mechanistic analyses showed that TMED2 and TMED10 are essential components of a multiprotein supercomplex that operates exchange of both cholesterol and ceramides at ER-Golgi membrane contact sites. Overall, this study of anthrax intoxication led to the discovery that lipid compositional remodelling at ER-Golgi interfaces fully controls the formation of functional membrane nanodomains at the cell surface.

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Section: Discussionmentioning

confidence: 99%

Anthrax intoxication reveals that ER-Golgi membrane contact sites control the formation of plasma membrane lipid nanodomains

Anwar

Sergeeva

Abrami

et al. 2022

Preprint

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“…The interaction between Vps13 and the Golgi membranes could also be established through Golgi-specific lipids. Purified Vps13 binds well to liposomes containing PI(4)P, the lipid produced and enriched in Golgi membranes [65,66]; the N-terminal region of Vps13 is responsible for this interaction [22]. We recently demonstrated that Vps13 and VPS13A possess the APT1 domain [19,20].…”

Section: Discussionmentioning

confidence: 99%

The GTPase Arf1 Is a Determinant of Yeast Vps13 Localization to the Golgi Apparatus

Kolakowski

Rzepnikowska

Kaniak-Golik

et al. 2021

IJMS

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VPS13 proteins are evolutionarily conserved. Mutations in the four human genes (VPS13A-D) encoding VPS13A-D proteins are linked to developmental or neurodegenerative diseases. The relationship between the specific localization of individual VPS13 proteins, their molecular functions, and the pathology of these diseases is unknown. Here we used a yeast model to establish the determinants of Vps13′s interaction with the membranes of Golgi apparatus. We analyzed the different phenotypes of the arf1-3 arf2Δ vps13∆ strain, with reduced activity of the Arf1 GTPase, the master regulator of Golgi function and entirely devoid of Vps13. Our analysis led us to propose that Vps13 and Arf1 proteins cooperate at the Golgi apparatus. We showed that Vps13 binds to the Arf1 GTPase through its C-terminal Pleckstrin homology (PH)-like domain. This domain also interacts with phosphoinositol 4,5-bisphosphate as it was bound to liposomes enriched with this lipid. The homologous domain of VPS13A exhibited the same behavior. Furthermore, a fusion of the PH-like domain of Vps13 to green fluorescent protein was localized to Golgi structures in an Arf1-dependent manner. These results suggest that the PH-like domains and Arf1 are determinants of the localization of VPS13 proteins to the Golgi apparatus in yeast and humans.

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“…Type II ARFs ARF1 and ARF3 are the sole ARFs localizing to TGN membranes After establishing the role of different ARFs in sorting at early secretory organelles, we next wanted to test their role in export from the TGN. As all ARFs have been implicated in post-Golgi trafficking (Adarska et al, 2021) we set out to understand which ones localize to the most distal TGN cisternae and to investigate their spatial relationship with the clathrin machinery. Firstly, the localization of the different ARF members endogenously tagged with 2xALFA was tested with the TGN marker Golgin97.…”

Section: Different Arf Isoforms Support Copi Recruitment On Different...mentioning

confidence: 99%

Gene editing and super-resolution microscopy reveal multiple distinct roles for ARF GTPases in cellular membrane organization

Wong-Dilworth

Rodilla-Ramirez

Fox

et al. 2022

Preprint

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ADP-ribosylation factor (ARF) GTPases are major regulators of cellular membrane homeostasis. High sequence similarity and multiple, possible redundant functions of the five human ARFs make investigating their function a challenging task. To shed light on the roles of the different Golgi-localized ARF members in membrane trafficking, we generated CRISPR-Cas9 knock ins (KIs) of type I (ARF1 and ARF3) and type II ARFs (ARF4 and ARF5) and mapped their nanoscale localization with stimulated emission depletion (STED) super-resolution microscopy. We find ARF1, ARF4 and ARF5 on segregated nano-domains on the cis-Golgi and ER-Golgi intermediate compartments (ERGIC), revealing distinct roles in COPI recruitment on early secretory membranes. Interestingly, ARF4 and ARF5 define Golgi-tethered ERGIC elements decorated by COPI and devoid of ARF1. Differential localization of ARF1 and ARF4 on distal ERGICs suggests the presence of functionally different classes of intermediate compartments that could regulate bi-directional transport between the ER and the Golgi. Furthermore, ARF1 and ARF3 localize to segregated nano-domains on the trans-Golgi network (TGN) and TGN-derived post-Golgi tubules, strengthening the idea of distinct roles in post-Golgi sorting. This work provides the first map of the nanoscale organization of human ARF GTPases on cellular membranes and sets the stage to dissect their numerous cellular roles.

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ARF GTPases and Their Ubiquitous Role in Intracellular Trafficking Beyond the Golgi

Cited by 55 publications

References 73 publications

Anthrax intoxication reveals that ER-Golgi membrane contact sites control the formation of plasma membrane lipid nanodomains

Anthrax intoxication reveals that ER-Golgi membrane contact sites control the formation of plasma membrane lipid nanodomains

The GTPase Arf1 Is a Determinant of Yeast Vps13 Localization to the Golgi Apparatus

Gene editing and super-resolution microscopy reveal multiple distinct roles for ARF GTPases in cellular membrane organization

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