Association of brefeldin A-inhibited guanine nucleotide-exchange protein 2 (BIG2) with recycling endosomes during transferrin uptake

Shen, X. Y.; Xu, Kai‐Feng; Fan, Qingyuan; Pacheco–Rodriguez, Gustavo; Moss, Joel; Vaughan, Martha

doi:10.1073/pnas.0510599103

Cited by 57 publications

(59 citation statements)

References 40 publications

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“…Depletion of BIG1 or BIG2 using specific siRNAs or overexpression of a dominant-negative GEF-inactive Sec7 domain mutant interfered with vesicular transport of specific proteins from TGN or recycling endosomes to the plasma membrane (24,27,28,41). Interference with β-catenin trafficking by expression of GEF-inactive BIG1 or BIG2, but not wild type (WT) or BIG1 AKAP mutant, led to its accumulation in perinuclear clusters (Fig.…”

Section: Resultsmentioning

confidence: 93%

“…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). Overexpression in cultured cells of mutant BIG2 lacking Arf GEF activity markedly altered intracellular distributions of E-cadherin and β-catenin (32).…”

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confidence: 99%

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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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Section: Resultsmentioning

confidence: 93%

mentioning

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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“…The ARF-GEF family is divided into several subfamilies; these include the brefeldin A (BFA)-sensitive GBF/BIG subfamily, whose members localize to and function at the Golgi apparatus, and can activate class I and class II ARFs (Jackson and Casanova, 2000;). We and others have shown that BIG2 activates class I ARFs (ARF1 and ARF3), localizes to recycling endosomes as well as the TGN, and is required for the integrity of recycling endosomes (Ishizaki et al, 2008;Shen et al, 2006;. However, it has not yet been clarified whether ARF1 and ARF3 participate in endosome integrity downstream of BIG2, in part because it is not yet known whether these ARFs are associated with endosomal compartments.…”

Section: Introductionmentioning

confidence: 99%

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

Kondo

Hanai

Nakai

et al. 2012

Cell Struct. Funct.

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ABSTRACT. Small GTPases ARF1 and ARF3 localize mainly to the Golgi apparatus, where they trigger formation of coated carrier vesicles. We previously showed that BIG2, a guanine nucleotide exchange factor specific for ARF1 and ARF3, localizes not only to the trans-Golgi network (TGN) but also to recycling endosomes, where it is involved in regulating the integrity of recycling endosomes. However, it is not yet clear whether ARF1 and ARF3 act downstream of BIG2 to ensure endosome integrity. In this study, we show that EGFP-tagged ARF1 and ARF3 localize to endosomal compartments containing endocytosed transferrin. We further demonstrate that simultaneous depletion of ARF1 and ARF3 induces tubulation of recycling endosomal compartments positive for transferrin receptor, Rab4, and Rab11, but does not significantly affect the integrity of the Golgi apparatus or early or late endosomes. Moreover, the simultaneous depletion of ARF1 and ARF3 suppresses recycling of transferrin but does not affect either its endocytosis or the retrograde transport of TGN38 from early/recycling endosomes to the TGN. In addition, depletion of ARF1 and ARF3 does not affect retrograde transport of CD4-furin from late endosomes to the TGN, or of endocytosed EGF from late endosomes to lysosomes. These results indicate that ARF1 and ARF3 are redundantly required for the integrity of recycling endosomes, and that they regulate transferrin recycling from endosomes to the plasma membrane, but not retrograde transport from endosomal compartments to the TGN.

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“…From the Sec7/BIG group BIG1 and BIG2 proteins were purified from bovine brain together with macromolecular complexes (>670 kDa) (Morinaga et al 1996). Several studies reported the association of BIG proteins with the trans-Golgi network (TGN) (Mansour et al 1999;Yamaji et al 2000;Shinotsuka et al 2002a,b;Zhao et al 2002), in addition, the association with recycling endosomes was also demonstrated Shen et al 2006). BIG1 and BIG2 proteins revealed considerable similarities to each other in the sequence and domain organization (Mouratou et al 2005), however, it is still not clear whether both proteins play redundant or distinct role in the control of membrane trafficking.…”

Section: Introductionmentioning

confidence: 99%

Early embryonic lethality in gene trap mice with disruption of the Arfgef2 gene

Grzmil

Enkhbaatar²,

Gundsambuu³

et al. 2010

Int. J. Dev. Biol.

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The switching of ADP-ribosylation factors from the inactive form to the active form is catalyzed by ARF-GEF (ADP ribosylation factor -guanine nucleotide exchange protein) proteins containing a Sec7 domain. The murine Arfgef2 gene encoding the BIG2 protein belongs to the class of high molecular mass (>100 kDa) ARF-GEF proteins. BIG2 is believed to be associated with the trans-Golgi network and the recycling endosomes. In humans, mutations in the ARFGEF2 gene cause autosomal recessive periventricular heterotopia with microcephaly. To elucidate the function of BIG2 in mouse we studied a gene-trap mouse line with a functional disruption of the Arfgef2 gene. Heterozygous mutants did not reveal phenotypic abnormalities and were fertile. However, no homozygous embryos were obtained from breeding heterozygous females and males. To explore the reason for embryonic lethality, we analysed the pattern of expression of Arfgef2. Arfgef2 transcripts were detected in several adult tissues. Interestingly, Arfgef2 undergoes alternative splicing and the splicing pattern differs among tissues from adult animals. Moreover, the LacZ reporter gene of the gene-trap construct was used to reveal the expression of Arfgef2 during embryonic development. Here, we show that Arfgef2 mRNA is stored in the oocyte and is likely translated during the first embryonic divisions. SNP (Single Nucleotide Polymorphism) markers were used to demonstrate that the embryonic Arfgef2 gene is activated first at the 4-cell stage, suggesting an important role for embryonic development. This assumption is supported by the failure of Arfgef2-deficient oocytes fertilized with Arfgef2-deficient sperm to develop into 4-cell stage embryos. Our results indicate that murine BIG2 is essential for early embryonic development.

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Association of brefeldin A-inhibited guanine nucleotide-exchange protein 2 (BIG2) with recycling endosomes during transferrin uptake

Cited by 57 publications

References 40 publications

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

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

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

Early embryonic lethality in gene trap mice with disruption of the Arfgef2 gene

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