Rab11-FIP1A regulates early trafficking into the recycling endosomes

Schafer, James A.; McRae, Rebecca; Manning, Elizabeth; Lapierre, Lynne A.; Goldenring, James R.

doi:10.1016/j.yexcr.2016.01.003

Cited by 19 publications

(12 citation statements)

References 40 publications

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“…We showed that the RFFL DN mutant failed to affect the internalization, but delayed the recycling of cargoes internalized by CME and CIE, and caused them to accumulate in the clustered ERC. This phenotype is reminiscent of that observed upon EHD1 knockdown (KD) (Jovićet al, 2007;Rapaport et al, 2006), MICALL1 KD (Sharma et al, 2009) and overexpression of class I Rab11-FIP mutants (Schafer et al, 2016;Ducharme et al, 2007) or the MYO5B tail (Hales et al, 2002). Thus, the RFFL DN mutant might compromise the function of these recycling machineries.…”

Section: Discussionmentioning

confidence: 90%

The integral function of the endocytic recycling compartment is regulated by RFFL-mediated ubiquitylation of Rab11 effectors

Sakai

Fukuda

Unida

et al. 2019

Journal of Cell Science

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Endocytic trafficking is regulated by ubiquitylation (also known as ubiquitination) of cargoes and endocytic machineries. The role of ubiquitylation in lysosomal delivery has been well documented, but its role in the recycling pathway is largely unknown. Here, we report that the ubiquitin (Ub) ligase RFFL regulates ubiquitylation of endocytic recycling regulators. An RFFL dominant-negative (DN) mutant induced clustering of endocytic recycling compartments (ERCs) and delayed endocytic cargo recycling without affecting lysosomal traffic. A BioID RFFL interactome analysis revealed that RFFL interacts with the Rab11 effectors EHD1, MICALL1 and class I Rab11-FIPs. The RFFL DN mutant strongly captured these Rab11 effectors and inhibited their ubiquitylation. The prolonged interaction of RFFL with Rab11 effectors was sufficient to induce the clustered ERC phenotype and to delay cargo recycling. RFFL directly ubiquitylates these Rab11 effectors in vitro, but RFFL knockout (KO) only reduced the ubiquitylation of Rab11-FIP1. RFFL KO had a minimal effect on the ubiquitylation of EHD1, MICALL1, and Rab11-FIP2, and failed to delay transferrin recycling. These results suggest that multiple Ub ligases including RFFL regulate the ubiquitylation of Rab11 effectors, determining the integral function of the ERC.

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Section: Discussionmentioning

confidence: 90%

The integral function of the endocytic recycling compartment is regulated by RFFL-mediated ubiquitylation of Rab11 effectors

Sakai

Fukuda

Unida

et al. 2019

Journal of Cell Science

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“…Manual curation added another 18 proteins with Rab11FIP1, Rab GTPase-binding effector protein 2 (RabEP2), ATP6V1B1, TBC1D13, sorting nexin-24 (SNX24), and synaptogyrin-2 (SYNGR2) being upregulated. Rab11FIP1 is a Rab-interacting protein that is critical for trafficking into early endosomes ( 55 ). TBC1D13, a Rab35-specific GAP that contributes to GLUT4 trafficking, was also upregulated ( 56 ), while CCT8, NISCH, and VAMP5 were downregulated ( Table S2 ).…”

Section: Resultsmentioning

confidence: 99%

Global Proteomic Changes Induced by the Epstein-Barr Virus Oncoproteins Latent Membrane Protein 1 and 2A

DeKroon

Gunawardena

Edwards

et al. 2018

mBio

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The Epstein-Barr virus (EBV) oncoproteins latent membrane protein 1 (LMP1) and LMP2A constitutively activate multiple signaling pathways, and both have been shown to interact with cellular ubiquitin ligases and affect cellular ubiquitination. To detect the LMP1- and LMP2A-mediated effects on the global cellular proteome, epithelial cell lines expressing LMP1 or LMP2A were analyzed using label-free quantitative proteomics. To identify proteins whose ubiquitination is affected by the viral proteins, the cells were cultured in the presence and absence of deubiquitinase (DUB) and proteasome inhibitors. More than 7,700 proteins were identified with high confidence and considerably more proteins showed significant differences in expression in the presence of inhibitors. Few of the differentially expressed proteins with or without inhibitors were common between LMP1 and LMP2A, confirming that the viral proteins induce unique changes in cell expression and function. However, ingenuity pathway analysis (IPA) of the data indicated that LMP1 and LMP2A modulate many of the same cellular regulatory pathways, including cell death and survival, cell movement, and actin filament dynamics. In addition, various proteasome subunits, ubiquitin-specific peptidases and conjugating enzymes, vesicle trafficking proteins, and NF-κB and mitogen-activated protein kinase signaling proteins were affected by LMP1 or LMP2A. These findings suggest that LMP1 and LMP2A may commonly target critical cell pathways through effects on distinct genes, with many cellular proteins modified by ubiquitination and/or degradation.

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“…As proper vesicular transport is essential for neuronal maintenance and survival, increase of related proteins such as RAB11-FIP which regulates endosomal trafficking [ 39 ] in MSS-LCs but not in both, vulnerable and non-vulnerable PCs of woozy (Figures 6B, 6C , 7E ), makes a neuroprotective role of this protein in MSS-pathogenesis unlikely.…”

Section: Resultsmentioning

confidence: 99%

In-depth phenotyping of lymphoblastoid cells suggests selective cellular vulnerability in Marinesco-Sjögren syndrome

et al. 2017

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SIL1 is a ubiquitous protein of the Endoplasmic Reticulum (ER) acting as a co-chaperone for the ER-resident chaperone, BiP. Recessive mutations of the corresponding gene lead to vulnerability of skeletal muscle and central nervous system in man (Marinesco-Sjögren syndrome; MSS) and mouse. However, it is still unclear how loss of ubiquitous SIL1 leads to selective vulnerability of the nervous system and skeletal muscle whereas other cells and organs are protected from clinical manifestations. In this study we aimed to disentangle proteins participating in selective vulnerability of SIL1-deficient cells and tissues: morphological examination of MSS patient-derived lymphoblastoid cells revealed altered organelle structures (ER, nucleus and mitochondria) thus showing subclinical vulnerability. To correlate structural perturbations with biochemical changes and to identify proteins potentially preventing phenotypical manifestation, proteomic studies have been carried out. Results of proteomic profiling are in line with the morphological findings and show affection of nuclear, mitochondrial and cytoskeletal proteins as well as of such responsible for cellular viability. Moreover, expression patterns of proteins known to be involved in neuromuscular disorders or in development and function of the nervous system were altered. Paradigmatic findings were confirmed by immunohistochemistry of splenic lymphocytes and the cerebellum of SIL1-deficient mice. Ataxin-10, identified with increased abundance in our proteome profile, is necessary for the neuronal survival but also controls muscle fiber apoptosis, thus declaring this protein as a plausible candidate for selective tissue vulnerability. Our combined results provide first insights into the molecular causes of selective cell and tissue vulnerability defining the MSS phenotype.

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Rab11-FIP1A regulates early trafficking into the recycling endosomes

Cited by 19 publications

References 40 publications

The integral function of the endocytic recycling compartment is regulated by RFFL-mediated ubiquitylation of Rab11 effectors

The integral function of the endocytic recycling compartment is regulated by RFFL-mediated ubiquitylation of Rab11 effectors

Global Proteomic Changes Induced by the Epstein-Barr Virus Oncoproteins Latent Membrane Protein 1 and 2A

In-depth phenotyping of lymphoblastoid cells suggests selective cellular vulnerability in Marinesco-Sjögren syndrome

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