The BRAG/IQSec family of Arf GEFs

D’Souza, Ryan S; Casanova, James E.

doi:10.1080/21541248.2016.1219442

Cited by 17 publications

(14 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…20,33,34 We previously demonstrated by immunohistochemistry using the anti-panBRAG2 antibody that BRAG2, a GEF specific for Arf6, colocalizes with the DGC at the photoreceptor presynaptic terminal. 18 In the present study, we produced a novel antibody that recognized the C-terminal region of BRAG2a and extended our previous finding by showing that BRAG2, especially BRAG2a, is a novel component of the DGC at the photoreceptor terminal using independent assays. First, both immunofluorescence and immunoelectron microscopy demonstrated that BRAG2a exhibited subcellular localization in the same subcompartment of the photoreceptor terminal as b-dystroglycan.…”

Section: Discussionsupporting

confidence: 49%

“…17,18 There are at least two alternative splicing isoforms, BRAG2a and BRAG2b, which share a conserved domain structure among the BRAG/IQSEC family, consisting of an N-terminal calmodulin-binding IQ-like motif, a central catalytic Sec7 domain, and a pleckstrin homology (PH) domain, but differ by the alternative use of N-terminal and Cterminal regions (Fig. 1A).…”

mentioning

confidence: 99%

See 1 more Smart Citation

BRAG2a, a Guanine Nucleotide Exchange Factor for Arf6, Is a Component of the Dystrophin-Associated Glycoprotein Complex at the Photoreceptor Terminal

Sakagami

Katsumata

Hara

et al. 2017

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Citation: Sakagami H, Katsumata O, Hara Y, Sasaoka T, Fukaya M. BRAG2a, a guanine nucleotide exchange factor for Arf6, is a component of the dystrophin-associated glycoprotein complex at the photoreceptor terminal. Invest Ophthalmol Vis Sci. 2017;58:3795-3803. DOI:10.1167/ iovs.17-21746 PURPOSE. Mutations in genes encoding the dystrophin-associated glycoprotein complex (DGC) can cause muscular dystrophy and disturb synaptic transmission in the photoreceptor ribbon synapse. However, the molecular composition and specific functions of the photoreceptor DGC remain unknown. Brefeldin A-resistant Arf-GEF 2 (BRAG2), also known as IQSEC1, is a guanine nucleotide exchange factor for ADP-ribosylation factor 6 (Arf6), a critical GTPase that regulates endosomal trafficking and actin cytoskeleton remodeling. In the present study, we characterized the expression of BRAG2a, an alternative splicing isoform of BRAG2, in the adult mouse photoreceptor. METHODS.Immunofluorescence and immunoelectron microscopic analyses of adult mouse retinas were performed using a novel anti-BRAG2a antibody. Pull-down, immunoprecipitation, and in situ proximity ligation assays were performed to examine the interaction between BRAG2a and the DGC in vivo. RESULTS.Immunofluorescence demonstrated punctate colocalization of BRAG2a with bdystroglycan in the outer plexiform layer. Immunoelectron microscopy revealed the localization of BRAG2a at the plasma membrane of lateral walls and processes of photoreceptor terminals within the synaptic cavity. Pull-down and immunoprecipitation assays using retinal lysates demonstrated the protein complex formation between BRAG2a with the DGC. In situ proximity ligation assays further detected a close spatial relationship between BRAG2a and b-dystroglycan in the outer plexiform layer.CONCLUSIONS. The present study provided evidence that BRAG2a is a novel component of the photoreceptor DGC, suggesting functional involvement of the BRAG2a-Arf6 pathway downstream of the DGC.

show abstract

Section: Discussionsupporting

confidence: 49%

mentioning

confidence: 99%

BRAG2a, a Guanine Nucleotide Exchange Factor for Arf6, Is a Component of the Dystrophin-Associated Glycoprotein Complex at the Photoreceptor Terminal

Sakagami

Katsumata

Hara

et al. 2017

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…One example is IQSec/BRAG, a GEF of the Arf family that is implicated in metastasis in different kinds of cancers. It has an IQ motif located at its N-terminus and is atypical for most CaM-binding proteins, as it binds Ca 2+ -free CaM (apo-CaM) and releases CaM upon Ca 2+ binding (reviewed in [193]).…”

Section: Cam-regulated Small G Proteinsmentioning

confidence: 99%

The Role of Calmodulin in Tumor Cell Migration, Invasiveness, and Metastasis

Villalobo

Berchtold

2020

IJMS

View full text Add to dashboard Cite

Calmodulin (CaM) is the principal Ca2+ sensor protein in all eukaryotic cells, that upon binding to target proteins transduces signals encoded by global or subcellular-specific changes of Ca2+ concentration within the cell. The Ca2+/CaM complex as well as Ca2+-free CaM modulate the activity of a vast number of enzymes, channels, signaling, adaptor and structural proteins, and hence the functionality of implicated signaling pathways, which control multiple cellular functions. A basic and important cellular function controlled by CaM in various ways is cell motility. Here we discuss the role of CaM-dependent systems involved in cell migration, tumor cell invasiveness, and metastasis development. Emphasis is given to phosphorylation/dephosphorylation events catalyzed by myosin light-chain kinase, CaM-dependent kinase-II, as well as other CaM-dependent kinases, and the CaM-dependent phosphatase calcineurin. In addition, the role of the CaM-regulated small GTPases Rac1 and Cdc42 (cell division cycle protein 42) as well as CaM-binding adaptor/scaffold proteins such as Grb7 (growth factor receptor bound protein 7), IQGAP (IQ motif containing GTPase activating protein) and AKAP12 (A kinase anchoring protein 12) will be reviewed. CaM-regulated mechanisms in cancer cells responsible for their greater migratory capacity compared to non-malignant cells, invasion of adjacent normal tissues and their systemic dissemination will be discussed, including closely linked processes such as the epithelial–mesenchymal transition and the activation of metalloproteases. This review covers as well the role of CaM in establishing metastatic foci in distant organs. Finally, the use of CaM antagonists and other blocking techniques to downregulate CaM-dependent systems aimed at preventing cancer cell invasiveness and metastasis development will be outlined.

show abstract

“…loner, also known as schizo, was identified in an EMS mutagenesis screen for myoblast fusion mutants (29). Loner is a member of the BRAG family of ADP-ribosylation factor (Arf) GEFs, which are known to activate the Arf GTPases at plasma membranes and endosomes (32). A function of Loner in founder cells is supported by its expanded expression in Notch mutant embryos that contain more founder cells, its localization at the vicinity of the founder cell nuclear marker rP298-lacZ, and its recruitment by Duf to cell contact sites in cultured Drosophila cells (29).…”

Section: Group I P21-activated Kinasesmentioning

confidence: 99%

DrosophilaMyoblast Fusion: Invasion and Resistance for the Ultimate Union

Lee

Chen

2019

Annu. Rev. Genet.

View full text Add to dashboard Cite

Cell–cell fusion is indispensable for creating life and building syncytial tissues and organs. Ever since the discovery of cell–cell fusion, how cells join together to form zygotes and multinucleated syncytia has remained a fundamental question in cell and developmental biology. In the past two decades, Drosophila myoblast fusion has been used as a powerful genetic model to unravel mechanisms underlying cell–cell fusion in vivo. Many evolutionarily conserved fusion-promoting factors have been identified and so has a surprising and conserved cellular mechanism. In this review, we revisit key findings in Drosophila myoblast fusion and highlight the critical roles of cellular invasion and resistance in driving cell membrane fusion.

show abstract

The BRAG/IQSec family of Arf GEFs

Cited by 17 publications

References 49 publications

BRAG2a, a Guanine Nucleotide Exchange Factor for Arf6, Is a Component of the Dystrophin-Associated Glycoprotein Complex at the Photoreceptor Terminal

BRAG2a, a Guanine Nucleotide Exchange Factor for Arf6, Is a Component of the Dystrophin-Associated Glycoprotein Complex at the Photoreceptor Terminal

The Role of Calmodulin in Tumor Cell Migration, Invasiveness, and Metastasis

DrosophilaMyoblast Fusion: Invasion and Resistance for the Ultimate Union

Contact Info

Product

Resources

About