ARF1 and ARF3 Are Required for the Integrity of Recycling Endosomes and the Recycling Pathway

Kondo, Yumika; Hanai, Ayako; Nakai, Waka; Katoh, Yohei; Nakayama, Kazuhisa; Shin, Hye‐Won

doi:10.1247/csf.12015

Cited by 61 publications

(65 citation statements)

References 50 publications

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“…We then treated doxycycline-induced LS174T-W4 cells with brefeldin A, an inhibitor of ADP-ribosylating factors (Arfs), which have previously been shown to control the organization of Rab11a-positive endosomes (Kondo et al, 2012;Shin et al, 2004). In brefeldin-A-treated cells, Mst4 was no longer enriched at the apical surface domain, but accumulated with Rab11a in distinct punctate structures (Fig.…”

Section: Resultsmentioning

confidence: 99%

Myosin Vb and rab11a regulate ezrin phosphorylation in enterocytes

Dhekne

Hsiao

Roelofs

et al. 2014

Journal of Cell Science

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Microvilli at the apical surface of enterocytes allow the efficient absorption of nutrients in the intestine. Ezrin activation by its phosphorylation at T567 is important for microvilli development, but how such ezrin phosphorylation is controlled is not well understood. We demonstrate that a subset of kinases that phosphorylate ezrin closely co-distributes with apical recycling endosome marker Rab11a in the subapical domain. Expression of dominant-negative Rab11a mutant or depletion of the Rab11a-binding motor protein myosin Vb prevents the subapical enrichment of Rab11a and these kinases and inhibits ezrin phosphorylation and microvilli development, without affecting the polarized distribution of ezrin itself. We observe a similar loss of the subapical enrichment of Rab11a and the kinases and reduced phosphorylation of ezrin in microvillus inclusion disease, which is associated with MYO5B mutations, intestinal microvilli atrophy and malabsorption. Thus, part of the machinery for ezrin activation depends on recycling endosomes controlled by myosin Vb and Rab11a which, we propose, might act as subapical signaling platforms that enterocytes use to regulate development of microvilli and maintain human intestinal function.

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Section: Resultsmentioning

confidence: 99%

Myosin Vb and rab11a regulate ezrin phosphorylation in enterocytes

Dhekne

Hsiao

Roelofs

et al. 2014

Journal of Cell Science

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“…1A) responsible for ADP-ribosylation factor (Arf) activation. Microscopically, BIG1 was seen mainly at the trans-Golgi network (TGN), sometimes partially overlapping BIG2, which was associated also with recycling endosomes (24-26), e.g., in moving proteins and lipids among TGN, endosomes, and cell surface (24,(27)(28)(29). Although actions of BIG1 and BIG2 at the TGN were described as "redundant" (27), each protein clearly has specific roles in moving proteins and lipids that are not shared with the other (24,30,31).…”

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confidence: 99%

Enhancement of β-catenin activity by BIG1 plus BIG2 via Arf activation and cAMP signals

Kang

Katō

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Multifunctional β-catenin, with critical roles in both cell-cell adhesion and Wnt-signaling pathways, was among HeLa cell proteins coimmunoprecipitated by antibodies against brefeldin A-inhibited guanine nucleotide-exchange factors 1 and 2 (BIG1 or BIG2) that activate ADP-ribosylation factors (Arfs) by accelerating the replacement of bound GDP with GTP. BIG proteins also contain A-kinase anchoring protein (AKAP) sequences that can act as scaffolds for multimolecular assemblies that facilitate and limit cAMP signaling temporally and spatially. Direct interaction of BIG1 N-terminal sequence with β-catenin was confirmed using yeast two-hybrid assays and in vitro synthesized proteins. Depletion of BIG1 and/or BIG2 or overexpression of guanine nucleotide-exchange factor inactive mutant, but not wild-type, proteins interfered with β-catenin trafficking, leading to accumulation at perinuclear Golgi structures. Both phospholipase D activity and vesicular trafficking were required for effects of BIG1 and BIG2 on β-catenin activation. Levels of PKAphosphorylated β-catenin S675 and β-catenin association with PKA, BIG1, and BIG2 were also diminished after BIG1/BIG2 depletion. Inferring a requirement for BIG1 and/or BIG2 AKAP sequence in PKA modification of β-catenin and its effect on transcription activation, we confirmed dependence of S675 phosphorylation and transcription coactivator function on BIG2 AKAP-C sequence.ADP-ribosylation factor | cell migration | AKAP | phospholipase D M ultifunctional β-catenin is an essential component of intercellular adherens junctions (AJs) that link cell surface cadherin and actin cytoskeleton via interactions with both. β-catenin is also a transcriptional coactivator in several pathways, including Wnt-initiated signaling (1, 2), which is critical in embryonic development and tissue homeostasis or pathology (2, 3). In the absence of "canonical" catenin-dependent Wnt signaling, cytoplasmic β-catenin is maintained at low levels via phosphorylations of S45 and S33, S37 and T41 by, respectively, casein kinase-1 and glycogen synthase kinase-3 (GSK-3) (1, 2). Subsequent degradation of β-catenin via an ubiquitin/proteasome pathway involves axin and adenomatous polyposis coli (APC) as scaffold proteins, plus β-transducin repeat-containing protein (β-TrCP), an E3 ubiquitin ligase. In one well-known model, binding of Wnt to Frizzled (Fz) and its coreceptor low-density lipoprotein receptor-like protein 5 or 6 (LRP5/6) resulted in GSK-3 sequestration in multivesicular bodies, thereby reducing its cytosolic level (4, 5). With lower GSK-3 activity, "stabilized" β-catenin (1, 2) entered the nucleus and, along with members of the T-cell factor (TCF)/lymphoid enhancer factor (LEF) family, activated transcription via Wnt-target gene promoters, including c-myc and cyclin D1 (6-8). In β-catenin knockout mice, embryogenesis was arrested at gastrulation (9) and aberrant Wnt signaling led to tumor development (2, 3).Although relationships between labile and stabilized β-catenin pools remain poorly understood, ...

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“…This means that only brefeldin A-sensitive class I ARF3 is involved in the TLR9 signaling pathway, rather than the entire class I ARF subfamily. These findings reveal that class I ARF1 does not have functions that are parallel with ARF3 in TLR9-mediated responses, despite both of them localizing chiefly to the Golgi complex and being redundantly required for the integrity of recycling endosomes [27] . We suppose that ARF3, but not ARF1, involvement in TLR9 signaling may be due to specific regulatory protein ARF-GEFs, which play a key role in inducing ARF activation.…”

Section: Discussionmentioning

confidence: 91%

ADP-Ribosylation Factor 3 Mediates Cytidine-Phosphate-Guanosine Oligodeoxynucleotide-Induced Responses by Regulating Toll-Like Receptor 9 Trafficking

Wu¹,

Kuo²

2015

J Innate Immun

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Toll-like receptor 9 (TLR9) trafficking from the endoplasmic reticulum (ER) into endolysosomes is critical for eliciting cytidine-phosphate-guanosine (CpG) DNA-mediated immune responses. ADP-ribosylation factor 3 (ARF3) is a member of the Ras superfamily, which is crucial for a wide variety of cellular events including protein trafficking. In this study, we found that the inhibition of ARF3 by dominant mutants and siRNA impaired CpG oligodeoxynucleotide (ODN)-mediated responses whereas cells expressing the constitutively active ARF3 mutant enhanced CpG ODN-induced NF-κB activation and cytokine production. Further experiments with MyD88-overexpressing fibroblast cells transfected with a dominant-negative mutant and a constitutively active mutant of ARF3 demonstrated that ARF3 regulated CpG ODN-mediated signaling upstream of MyD88. Additional studies have shown that ARF3 inhibition impairs TLR9 trafficking from the ER into endolysosomes, thereby inhibiting the functional cleavage of TLR9, although it has no significant effect on CpG ODN uptake. Furthermore, activated ARF3 is associated with Unc93B1 and TLR9, suggesting that ARF3 conducts TLR9 trafficking by forming the TLR9-Unc93B1-ARF3 complex. Overall, our findings demonstrate that a novel ARF3 axis pathway mediates CpG ODN-induced responses by regulating TLR9 trafficking.

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ARF1 and ARF3 Are Required for the Integrity of Recycling Endosomes and the Recycling Pathway

Cited by 61 publications

References 50 publications

Myosin Vb and rab11a regulate ezrin phosphorylation in enterocytes

Myosin Vb and rab11a regulate ezrin phosphorylation in enterocytes

Enhancement of β-catenin activity by BIG1 plus BIG2 via Arf activation and cAMP signals

ADP-Ribosylation Factor 3 Mediates Cytidine-Phosphate-Guanosine Oligodeoxynucleotide-Induced Responses by Regulating Toll-Like Receptor 9 Trafficking

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