scholarly journals ADP-ribosylation factor–like 4C binding to filamin-A modulates filopodium formation and cell migration

2017 ◽  
Vol 28 (22) ◽  
pp. 3013-3028 ◽  
Author(s):  
Tsai-Shin Chiang ◽  
Hsu-Feng Wu ◽  
Fang-Jen S. Lee
Keyword(s):  
Cell Migration ◽  
Morphological Changes ◽  
Small Gtpase ◽  
Dependent Manner ◽  
Filamin A ◽  
Filamentous Actin ◽  
Adp Ribosylation ◽  
Gtpase Activation ◽  
Adp Ribosylation Factor ◽  
Filopodium Formation

Changes in cell morphology and the physical forces that occur during migration are generated by a dynamic filamentous actin cytoskeleton. The ADP-ribosylation factor–like 4C (Arl4C) small GTPase acts as a molecular switch to regulate morphological changes and cell migration, although the mechanism by which this occurs remains unclear. Here we report that Arl4C functions with the actin regulator filamin-A (FLNa) to modulate filopodium formation and cell migration. We found that Arl4C interacted with FLNa in a GTP-dependent manner and that FLNa IgG repeat 22 is both required and sufficient for this interaction. We also show that interaction between FLNa and Arl4C is essential for Arl4C-induced filopodium formation and increases the association of FLNa with Cdc42-GEF FGD6, promoting cell division cycle 42 (Cdc42) GTPase activation. Thus our study revealed a novel mechanism, whereby filopodium formation and cell migration are regulated through the Arl4C-FLNa–mediated activation of Cdc42.

scholarly journals ADP-ribosylation factor–like 4A interacts with Robo1 to promote cell migration by regulating Cdc42 activation

2019 ◽  
Vol 30 (1) ◽  
pp. 69-81 ◽  
Author(s):  
Tsai-Shin Chiang ◽  
Ming-Chieh Lin ◽  
Meng-Chen Tsai ◽  
Chieh-Hsin Chen ◽  
Li-Ting Jang ◽  
...  
Keyword(s):  
Cell Migration ◽  
Molecular Mechanisms ◽  
Small Gtpase ◽  
Dependent Manner ◽  
Amino Acid Residues ◽  
Adp Ribosylation ◽  
Promote Cell Migration ◽  
Cytoskeleton Remodeling ◽  
Adp Ribosylation Factor

Cell migration is a highly regulated event that is initiated by cell membrane protrusion and actin reorganization. Robo1, a single-pass transmembrane receptor, is crucial for neuronal guidance and cell migration. ADP-ribosylation factor (Arf)–like 4A (Arl4A), an Arf small GTPase, functions in cell morphology, cell migration, and actin cytoskeleton remodeling; however, the molecular mechanisms of Arl4A in cell migration are unclear. Here, we report that the binding of Arl4A to Robo1 modulates cell migration by promoting Cdc42 activation. We found that Arl4A interacts with Robo1 in a GTP-dependent manner and that the Robo1 amino acid residues 1394–1398 are required for this interaction. The Arl4A-Robo1 interaction is essential for Arl4A-induced cell migration and Cdc42 activation but not for the plasma membrane localization of Robo1. In addition, we show that the binding of Arl4A to Robo1 decreases the association of Robo1 with the Cdc42 GTPase-activating protein srGAP1. Furthermore, Slit2/Robo1 binding down-regulates the Arl4A-Robo1 interaction in vivo, thus attenuating Cdc42-mediated cell migration. Therefore, our study reveals a novel mechanism by which Arl4A participates in Slit2/Robo1 signaling to modulate cell motility by regulating Cdc42 activity.

scholarly journals Recombinant protein of Haemonchus contortus small GTPase ADP-ribosylation factor 1 (HcARF1) modulate the cell mediated immune response in vitro

Oncotarget ◽  
2017 ◽  
Vol 8 (68) ◽  
pp. 112211-112221 ◽  
Author(s):  
Javaid Ali Gadahi ◽  
Muhammad Ehsan ◽  
Shuai Wang ◽  
Zhenchao Zhang ◽  
Ruofeng Yan ◽  
...  
Keyword(s):  
Immune Response ◽  
Recombinant Protein ◽  
Haemonchus Contortus ◽  
Small Gtpase ◽  
Adp Ribosylation ◽  
Cell Mediated Immune Response ◽  
Adp Ribosylation Factor ◽  
Immune Response In Vitro

scholarly journals ADP-Ribosylation Factor 6 Regulates Mammalian Myoblast Fusion through Phospholipase D1 and Phosphatidylinositol 4,5-Bisphosphate Signaling Pathways

2010 ◽  
Vol 21 (14) ◽  
pp. 2412-2424 ◽  
Author(s):  
Anne-Sophie Bach ◽  
Sandrine Enjalbert ◽  
Franck Comunale ◽  
Stéphane Bodin ◽  
Nicolas Vitale ◽  
...  
Keyword(s):  
Myoblast Fusion ◽  
Myoblast Differentiation ◽  
C2c12 Myoblast ◽  
Nucleotide Exchange ◽  
Adp Ribosylation ◽  
Rac1 Activity ◽  
Phospholipase D1 ◽  
Rac1 Gtpase ◽  
Gtpase Activation ◽  
Adp Ribosylation Factor

Myoblast fusion is an essential step during myoblast differentiation that remains poorly understood. M-cadherin–dependent pathways that signal through Rac1 GTPase activation via the Rho-guanine nucleotide exchange factor (GEF) Trio are important for myoblast fusion. The ADP-ribosylation factor (ARF)6 GTPase has been shown to bind to Trio and to regulate Rac1 activity. Moreover, Loner/GEP100/BRAG2, a GEF of ARF6, has been involved in mammalian and Drosophila myoblast fusion, but the specific role of ARF6 has been not fully analyzed. Here, we show that ARF6 activity is increased at the time of myoblast fusion and is required for its implementation in mouse C2C12 myoblasts. Specifically, at the onset of myoblast fusion, ARF6 is associated with the multiproteic complex that contains M-cadherin, Trio, and Rac1 and accumulates at sites of myoblast fusion. ARF6 silencing inhibits the association of Trio and Rac1 with M-cadherin. Moreover, we demonstrate that ARF6 regulates myoblast fusion through phospholipase D (PLD) activation and phosphatidylinositol 4,5-bis-phosphate production. Together, these data indicate that ARF6 is a critical regulator of C2C12 myoblast fusion and participates in the regulation of PLD activities that trigger both phospholipids production and actin cytoskeleton reorganization at fusion sites.

scholarly journals Cross-Kingdom Activation of Vibrio Toxins by ADP-Ribosylation Factor Family GTPases

2020 ◽  
Vol 202 (24) ◽  
Author(s):  
Alfa Herrera ◽  
Karla J. F. Satchell
Keyword(s):  
Vibrio Vulnificus ◽  
Bacterial Species ◽  
Small Gtpases ◽  
Small Gtpase ◽  
Cell Organelle ◽  
Content Type ◽  
Adp Ribosylation ◽  
Cellular Processes ◽  
Adp Ribosyltransferase ◽  
Adp Ribosylation Factor

ABSTRACT Pathogenic Vibrio species use many different approaches to subvert, attack, and undermine the host response. The toxins they produce are often responsible for the devastating effects associated with their diseases. These toxins target a variety of host proteins, which leads to deleterious effects, including dissolution of cell organelle integrity and inhibition of protein secretion. Becoming increasingly prevalent as cofactors for Vibrio toxins are proteins of the small GTPase families. ADP-ribosylation factor small GTPases (ARFs) in particular are emerging as a common host cofactor necessary for full activation of Vibrio toxins. While ARFs are not the direct target of Vibrio cholerae cholera toxin (CT), ARF binding is required for its optimal activity as an ADP-ribosyltransferase. The makes caterpillars floppy (MCF)-like and the domain X (DmX) effectors of the Vibrio vulnificus multifunctional autoprocessing repeats-in-toxin (MARTX) toxin also both require ARFs to initiate autoprocessing and activation as independent effectors. ARFs are ubiquitously expressed in eukaryotes and are key regulators of many cellular processes, and as such they are ideal cofactors for Vibrio pathogens that infect many host species. In this review, we cover in detail the known Vibrio toxins that use ARFs as cross-kingdom activators to both stimulate and optimize their activity. We further discuss how these contrast to toxins and effectors from other bacterial species that coactivate, stimulate, or directly modify host ARFs as their mechanisms of action.

scholarly journals ADP-ribosylation factor 6 modulates adrenergic stimulated lipolysis in adipocytes

2010 ◽  
Vol 298 (4) ◽  
pp. C921-C928 ◽  
Author(s):  
Yingqiu Liu ◽  
Dequan Zhou ◽  
Nada A. Abumrad ◽  
Xiong Su
Keyword(s):  
Glucose Transporter ◽  
Specific Inhibitor ◽  
Small Gtpase ◽  
Receptor Trafficking ◽  
Endocytic Pathway ◽  
Mrna Levels ◽  
Adrenergic Stimulation ◽  
Adp Ribosylation ◽  
Adp Ribosylation Factor

ADP-ribosylation factor 6 (Arf6) is a small GTPase that influences membrane receptor trafficking and the actin cytoskeleton. In adipocytes, Arf6 regulates the trafficking of the glucose transporter type 4 (GLUT4) and consequently insulin-stimulated glucose transport. Previous studies also indicated a role of Arf6 in adrenergic receptor trafficking, but whether this contributes to the control of lipolysis in adipocytes remains unknown. This was examined in the present study by using RNA interference (RNAi) and pharmaceutical inhibition in murine cultured 3T3-L1 adipocytes. Downregulation of Arf6 by RNAi impairs isoproterenol-stimulated lipolysis specifically but does not alter triacylglycerol (TAG) synthesis or the insulin signaling pathway. Neither total TAG amounts nor TAG fatty acid compositions are altered. The inhibitory effect on lipolysis is mimicked by dynasore, a specific inhibitor for dynamin, which is required for endocytosis. In contrast, lipolysis triggered by reagents that bypass events at the plasma membrane (e.g., forskolin, isobutylmethylxanthine or 8-bromo-cAMP) is not affected. Moreover, Arf6 protein levels in white adipose tissues are markedly increased in ob/ob mice, whereas they are decreased in obesity-resistant CD36 null mice. These changes reflect at least in part alterations in Arf6 mRNA levels. Collectively, these results suggest a role of the endocytic pathway and its regulation by Arf6 in adrenergic stimulation of lipolysis in adipocytes and potentially in the development of obesity.

scholarly journals c-Src-Mediated Phosphorylation of TRIP6 Regulates Its Function in Lysophosphatidic Acid-Induced Cell Migration

2005 ◽  
Vol 25 (14) ◽  
pp. 5859-5868 ◽  
Author(s):  
Yun-Ju Lai ◽  
Chen-Shan Chen ◽  
Weei-Chin Lin ◽  
Fang-Tsyr Lin
Keyword(s):  
Cell Migration ◽  
Lysophosphatidic Acid ◽  
Morphological Changes ◽  
Focal Adhesions ◽  
Dependent Manner ◽  
3T3 Cells ◽  
Erk Activation ◽  
Nih 3T3 ◽  
In Cells

ABSTRACT TRIP6 (thyroid receptor-interacting protein 6), also known as ZRP-1 (zyxin-related protein 1), is a member of the zyxin family that has been implicated in cell motility. Previously we have shown that TRIP6 binds to the LPA2 receptor and associates with several components of focal complexes in an agonist-dependent manner and, thus, enhances lysophosphatidic acid (LPA)-induced cell migration. Here we further report that the function of TRIP6 in LPA signaling is regulated by c-Src-mediated phosphorylation of TRIP6 at the Tyr-55 residue. LPA stimulation induces tyrosine phosphorylation of endogenous TRIP6 in NIH 3T3 cells and c-Src-expressing fibroblasts, which is virtually eliminated in Src-null fibroblasts. Strikingly, both phosphotyrosine-55 and proline-58 residues of TRIP6 are required for Crk binding in vitro and in cells. Mutation of Tyr-55 to Phe does not alter the ability of TRIP6 to localize at focal adhesions or associate with actin. However, it abolishes the association of TRIP6 with Crk and p130cas in cells and significantly reduces the function of TRIP6 to promote LPA-induced ERK activation. Ultimately, these signaling events control TRIP6 function in promoting LPA-induced morphological changes and cell migration.

scholarly journals Arl4D-EB1 interaction promotes centrosomal recruitment of EB1 and microtubule growth

2020 ◽  
Vol 31 (21) ◽  
pp. 2348-2362
Author(s):  
Shin-Jin Lin ◽  
Chun-Fang Huang ◽  
Tsung-Sheng Wu ◽  
Chun-Chun Li ◽  
Fang-Jen S. Lee
Keyword(s):  
Small Gtpase ◽  
Adp Ribosylation ◽  
Microtubule Growth ◽  
Adp Ribosylation Factor

The GTP-bound form of ADP-ribosylation factor-like 4D (Arl4D) small GTPase localizes to the centrosome and interacts with microtubule (MT) end-binding 1 (EB1) protein. Arl4D-EB1 interaction promotes EB1 centrosomal recruitment and increases the association of EB1 and p150 subunit of dynactin, thereby contributing to the nucleation of MTs at the centrosome.

scholarly journals Arf family GTP loading is activated by, and generates, positive membrane curvature

2008 ◽  
Vol 414 (2) ◽  
pp. 189-194 ◽  
Author(s):  
Richard Lundmark ◽  
Gary J. Doherty ◽  
Yvonne Vallis ◽  
Brian J. Peter ◽  
Harvey T. McMahon
Keyword(s):  
G Proteins ◽  
Membrane Curvature ◽  
Regulatory Proteins ◽  
Dependent Manner ◽  
Amphipathic Helix ◽  
Effector Molecules ◽  
Adp Ribosylation ◽  
Cellular Processes ◽  
Adp Ribosylation Factor ◽  
Small G Proteins

Small G-proteins belonging to the Arf (ADP-ribosylation factor) family serve as regulatory proteins for numerous cellular processes through GTP-dependent recruitment of effector molecules. In the present study we demonstrate that proteins in this family regulate, and are regulated by, membrane curvature. Arf1 and Arf6 were shown to load GTP in a membrane-curvature-dependent manner and stabilize, or further facilitate, changes in membrane curvature through the insertion of an amphipathic helix.

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