RUFY1 binds Arl8b and mediates endosome-to-TGN CI-M6PR retrieval for cargo sorting to lysosomes

Rawat, Shalini; Chatterjee, Dhruba J.; Marwaha, Rituraj; Charak, Gitanjali; Kumar, Gaurav; Shaw, Shrestha; Khatter, Divya; Heus, Cecilia de; Liv, Nalan; Klumperman, Judith; Tuli, Amit; Sharma, Mahak

doi:10.1083/jcb.202108001

Cited by 10 publications

(12 citation statements)

References 72 publications

(123 reference statements)

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“…2a). At steady-state, Rab14 was detected throughout the cell in small, sorting/recycling endosomes-like vesicles 22, 56 with a major concentration in the perinuclear area, as previously described 17 . Acute treatment with PJ34 altered Rab14 localization, which mostly accumulated in vesicles dispersed at the cell periphery (Fig.…”

Section: Resultssupporting

confidence: 63%

“…Of particular interest in this context is a recent study showing that GTP-Rab14 is required for RUFY1 localization at early/sorting endosomes, where RUFY1 binds the dynein/dynactin complex to allow endosome progression along microtubules 56 . These findings support our data showing a key role of MARylated Rab14 in endosomal progression, pointing at a novel PTM central to the process.…”

Section: Discussionmentioning

confidence: 99%

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The endocytic recycling pathway is controlled by the ADP-ribosylated GTPase Rab14

Corteggio

Monte

Schembri

et al. 2022

Preprint

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The GTPase Rab14 is localized at the trans-Golgi network and at the intermediate compartment associated to sorting/recycling endosomes-like structures of the transferrin- recycling pathway: as other Rab family members, it is involved in the regulation of intracellular vesicle trafficking, though its role and functional relationship with effector/endosomal proteins is still incomplete. We have analysed whether post-translational modifications could affect Rab14 activity: the results obtained define mono-ADP-ribosylation (MARylation) as the yet-unknown Rab14 modification, catalysed by the ADP-ribosyltransferase PARP12, which specifically modifies glutamic acid residues in position 159/162. This modification is essential for the Rab14- dependent endosome progression. Accordingly, recycling of the transferrin receptor is inhibited when MARylation of Rab14 is prevented by PARP12 knocking-down or inhibition, or by overexpression of Rab14 ADP-ribosylation-defective mutant. Under these conditions, Rab14 and transferrin receptors are withheld at the cell periphery at the level of the Rab4- RUFY1-positive sorting endosomes, indicating that the interaction of Rab14 with the dual effectors RUFY and then FIP1c (which specifically binds both Rab11 and Rab14) determines the progression between the Rab4-RUFY- and Rab11-FIP1c-specific vesicles. Therefore Rab14-MARylation determines the sequential binding of this GTPase to RUFY and FIP1c, thus controlling endosome progression (i.e., transferrin receptors recycling) through the Rab4- , Rab14- and Rab11-specific vesicles. This identifies a Rab14-specific compartment of the recycling pathway and a crucial enzymatic reaction amenable to pharmacological control.

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Section: Resultssupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

The endocytic recycling pathway is controlled by the ADP-ribosylated GTPase Rab14

Corteggio

Monte

Schembri

et al. 2022

Preprint

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“…The growing body of work on time-lapse measurements of organelle dynamics provides an alternative to fixed-cell imaging methods. For instance, recent experiments have reported real-time organelle dynamics in Drosophila [25], Hela cells [26, 27], Neurons [28]. These experiments contain information about organelle abundance; note that counting individual organelle copies from time-lapse videos is challenging [29].…”

Section: Discussionmentioning

confidence: 99%

Temporal Regulation of Organelle Biogenesis

Dixit¹,

Aniruddha²,

Choubey³

2022

Preprint

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Organelle abundance is tightly regulated in eukaryotic cells in response to external stimuli. The underlying mechanisms responsible for this regulation remains less understood. Time-lapse imaging of fluorescently labelled organelles allow for counting individual organelle copies at a single-cell level. These experiments contain information about the time evolution of distribution of organelle number across a population of cells. To tap onto such data, we build upon a recently proposed kinetic model of organelle biogenesis that explicitly incorporates de novo synthesis, fission, fusion and degradation of organelles. Different limits of this general model correspond to distinct mechanisms of organelle biogenesis. We compute the first two moments of organelle number distribution for these different mechanisms. Interestingly, different mechanisms of biogenesis lead to qualitatively distinct temporal behavior of cell-to-cell variability (noise), thereby allowing us to discern between these mechanisms. Notably, noise in temporal organelle abundance exhibits strikingly more complex behaviour as compared to the steady state. Our modeling framework paves the way for extracting quantitative information about the dynamics of organelle biogenesis from time-lapse experiments that can measure organelle abundance at single-molecule resolution.

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“…[ 33 ] RUFY1 and RUFY3 incorporate with Arl8 to shift the endolysosomes from the axon to retrograde direction in neurons, and promote the endolysosome clustering in perinuclear region in non‐neuronal cells. [ 126,127 ] Taken together, Arl8 regulates both cellular anterograde and retrograde transport of lysosomes in the kinesin‐ and dynein‐dependent manner, respectively.…”

Section: Regulation Of Lysosomes Fusion and Transportmentioning

confidence: 99%

“…Recent studies reveal that RUN-and FYVE-domaincontaining proteins RUFY1 and RUFY3 act as Arl8 effectors, coupling the lysosomes to the dynein complex for retrograde transport. [125][126][127] An Arf-miniTurboID screening shows that RUFY1 and RUFY3 are significant hits in the proximity network of Arl8a and Arl8b. [33] RUFY1 and RUFY3 incorporate with Arl8 to shift the endolysosomes from the axon to retrograde direction in neurons, and promote the endolysosome clustering in perinuclear region in non-neuronal cells.…”

Section: Regulation Of Lysosomes Fusion and Transportmentioning

confidence: 99%

The Arf family GTPases: Regulation of vesicle biogenesis and beyond

Guan

2023

BioEssays

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The Arf family proteins are best known for their roles in the vesicle biogenesis. However, they also play fundamental roles in a wide range of cellular regulation besides vesicular trafficking, such as modulation of lipid metabolic enzymes, cytoskeleton remodeling, ciliogenesis, lysosomal, and mitochondrial morphology and functions. Growing studies continue to expand the downstream effector landscape of Arf proteins, especially for the less‐studied members, revealing new biological functions, such as amino acid sensing. Experiments with cutting‐edge technologies and in vivo functional studies in the last decade help to provide a more comprehensive view of Arf family functions. In this review, we summarize the cellular functions that are regulated by at least two different Arf members with an emphasis on those beyond vesicle biogenesis.

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RUFY1 binds Arl8b and mediates endosome-to-TGN CI-M6PR retrieval for cargo sorting to lysosomes

Cited by 10 publications

References 72 publications

The endocytic recycling pathway is controlled by the ADP-ribosylated GTPase Rab14

The endocytic recycling pathway is controlled by the ADP-ribosylated GTPase Rab14

Temporal Regulation of Organelle Biogenesis

The Arf family GTPases: Regulation of vesicle biogenesis and beyond

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