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.

scholarly journals Small G proteins in peroxisome biogenesis: the potential involvement of ADP-ribosylation factor 6

2009 ◽  
Vol 10 (1) ◽  
pp. 58 ◽  
Author(s):  
Erin A Anthonio ◽  
Chantal Brees ◽  
Eveline Baumgart-Vogt ◽  
Tsunaki Hongu ◽  
Sofie J Huybrechts ◽  
...  
Keyword(s):  
G Proteins ◽  
Peroxisome Biogenesis ◽  
Adp Ribosylation ◽  
Adp Ribosylation Factor ◽  
Small G Proteins

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 Roco Proteins and the Parkinson’s Disease-Associated LRRK2

2018 ◽  
Vol 19 (12) ◽  
pp. 4074 ◽  
Author(s):  
Jingling Liao ◽  
Quyen Hoang
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
G Proteins ◽  
Conformational Changes ◽  
Effector Proteins ◽  
Cellular Processes ◽  
Current State ◽  
Specific Effector ◽  
Unique Domain ◽  
Small G Proteins

Small G-proteins are structurally-conserved modules that function as molecular on-off switches. They function in many different cellular processes with differential specificity determined by the unique effector-binding surfaces, which undergo conformational changes during the switching action. These switches are typically standalone monomeric modules that form transient heterodimers with specific effector proteins in the ‘on’ state, and cycle to back to the monomeric conformation in the ‘off’ state. A new class of small G-proteins called “Roco” was discovered about a decade ago; this class is distinct from the typical G-proteins in several intriguing ways. Their switch module resides within a polypeptide chain of a large multi-domain protein, always adjacent to a unique domain called COR, and its effector kinase often resides within the same polypeptide. As such, the mechanisms of action of the Roco G-proteins are likely to differ from those of the typical G-proteins. Understanding these mechanisms is important because aberrant activity in the human Roco protein LRRK2 is associated with the pathogenesis of Parkinson’s disease. This review provides an update on the current state of our understanding of the Roco G-proteins and the prospects of targeting them for therapeutic purposes.

scholarly journals Small G proteins as key regulators of pancreatic digestive enzyme secretion

2009 ◽  
Vol 296 (3) ◽  
pp. E405-E414 ◽  
Author(s):  
John A. Williams ◽  
Xuequn Chen ◽  
Maria E. Sabbatini
Keyword(s):  
G Proteins ◽  
Secretory Granule ◽  
Secretory Pathway ◽  
Digestive Enzyme ◽  
Pancreatic Acinar Cells ◽  
Cellular Processes ◽  
Granule Membrane ◽  
Target Membrane ◽  
Rho Family ◽  
Small G Proteins

Small GTP-binding (G) proteins act as molecular switches to regulate a number of cellular processes, including vesicular transport. Emerging evidence indicates that small G proteins regulate a number of steps in the secretion of pancreatic acinar cells. Diverse small G proteins have been localized at discrete compartments along the secretory pathway and particularly on the secretory granule. Rab3D, Rab27B, and Rap1 are present on the granule membrane and play a role in the steps leading up to exocytosis. Whether the function of these G proteins is simply to ensure appropriate targeting or if they are involved as regulatory molecules is discussed. Most evidence suggests that Rab3D and Rab27B play a role in tethering the secretory granule to its target membrane. Other Rabs have been identified on the secretory granule that are associated with different steps in the secretory pathway. The Rho family small G proteins RhoA and Rac1 also regulate secretion through remodeling of the actin cytoskeleton. Possible mechanisms for regulation of these G proteins and their effector molecules are considered.

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 Differential cholera-toxin- and pertussis-toxin-catalysed ADP-ribosylation of G-proteins coupled to formyl-peptide and leukotriene B4 receptors

1993 ◽  
Vol 289 (2) ◽  
pp. 469-473 ◽  
Author(s):  
T M Schepers ◽  
K R McLeish
Keyword(s):  
Cholera Toxin ◽  
G Proteins ◽  
Pertussis Toxin ◽  
Leukotriene B4 ◽  
Guanine Nucleotides ◽  
Dependent Manner ◽  
Functional Responses ◽  
Concentration Dependent Manner ◽  
Adp Ribosylation ◽  
Formyl Peptide

N-Formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe) and leukotriene B4 (LTB4) induce disparate second-messenger generation and functional responses in neutrophils and HL-60 granulocytes. Receptors for these chemoattractants couple to a common pool of G-proteins which are substrates for both pertussis-toxin- and cholera-toxin-catalysed ADP-ribosylation. The hypothesis that formyl-peptide and LTB4 receptors induce different receptor-specific conformations of activated G-proteins was tested. The ability of pertussis toxin and cholera toxin to ADP-ribosylate G(i) proteins coupled to formyl-peptide or LTB4 receptors in membranes isolated from HL-60 granulocytes was used to assess the conformational state of the alpha subunits. Cholera-toxin-catalysed ADP-ribosylation of alpha 40 (40 kDa alpha subunit) was inhibited by guanosine 5′-[beta gamma-imido]triphosphate and GDP in a concentration-dependent manner. Addition of fMet-Leu-Phe, but not LTB4, re-established cholera-toxin labelling of alpha 40 in the presence of either guanine nucleotide. In the absence of guanine nucleotides, fMet-Leu-Phe and C5a enhanced cholera-toxin-catalysed labelling of alpha 40, whereas LTB4 and platelet-activating factor had no effect. Preincubation with fMet-Leu-Phe, but not LTB4, inhibited pertussis-toxin labelling of alpha 40 in the presence of guanosine 5′-[gamma-thio]triphosphate and in the absence of guanine nucleotides. Preincubation with fMet-Leu-Phe or LTB4 enhanced pertussis-toxin labelling of alpha 40 in the presence of GDP. These data suggest that activated G(i) proteins coupled to formyl-peptide and LTB4 receptors exist in different conformations determined by the receptor with which they interact.

scholarly journals Structure of small G proteins and their regulators.

2001 ◽  
Vol 48 (4) ◽  
pp. 829-850 ◽  
Author(s):  
M Paduch ◽  
F Jeleń ◽  
J Otlewski
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Protein Interactions ◽  
Sequence Similarity ◽  
Nucleotide Exchange ◽  
Microtubule Organization ◽  
Cellular Processes ◽  
Guanine Nucleotide Exchange ◽  
Small G Protein ◽  
Small G Proteins

In recent years small G proteins have become an intensively studied group of regulatory GTP hydrolases involved in cell signaling. More than 100 small G proteins have been identified in eucaryotes from protozoan to human. The small G protein superfamily includes Ras, Rho Rab, Rac, Sarl/Arf and Ran homologs, which take part in numerous and diverse cellular processes, such as gene expression, cytoskeleton reorganization, microtubule organization, and vesicular and nuclear transport. These proteins share a common structural core, described as the G domain, and significant sequence similarity. In this paper we review the available data on G domain structure, together with a detailed analysis of the mechanism of action. We also present small G protein regulators: GTPase activating proteins that bind to a catalytic G domain and increase its low intrinsic hydrolase activity, GTPase dissociation inhibitors that stabilize the GDP-bound, inactive state of G proteins, and guanine nucleotide exchange factors that accelerate nucleotide exchange in response to cellular signals. Additionally, in this paper we describe some aspects of small G protein interactions with down-stream effectors.

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.

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