Rab and Arf proteins at the crossroad between membrane transport and cytoskeleton dynamics

Kjos, Ingrid; Vestre, Katharina; Guadagno, Noemi Antonella; Distefano, Marita Borg; Progida, Cinzia

doi:10.1016/j.bbamcr.2018.07.009

Cited by 51 publications

(59 citation statements)

References 225 publications

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“…Quantitative assays strengthened the hypothesis of the movement of EhRabB and EhCPADH in membranes (Figure ). The movement of proteins through cellular membranes has been also reported for the EhRFN (fibronectin receptor; Hernandez‐Ramirez et al, ) and for other proteins (de Curtis & Meldolesi, ; Kjos et al, ).…”

Section: Discussionmentioning

confidence: 75%

“…The EhCPADH complex is involved in vesicle trafficking. As in other eukaryotes, in trophozoites, cytoskeleton is fundamental for vesicle transport, cell structure, and shape maintenance and motility (Franker & Hoogenraad, ; Kjos, Vestre, Guadagno, Borg Distefano, & Progida, ; Tolic‐Norrelykke, ). In this concerted movement, EhRab‐GTPase proteins transport functional molecules to different cellular compartments (Javier‐Reyna et al, ; Mitra, Saito‐Nakano, Nakada‐Tsukui, Sato, & Nozaki, ).…”

Section: Introductionmentioning

confidence: 99%

“…In eukaryotes, Rab GTPases modulate the vesicular transport through the cytoskeleton (Franker & Hoogenraad, ; Kjos et al, ; Tolic‐Norrelykke, ). They are molecular switches that present conformational changes associated with the GTP/GDP‐binding cycle.…”

Section: Introductionmentioning

confidence: 99%

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EhRabB mobilises the EhCPADH complex through the actin cytoskeleton during phagocytosis of Entamoeba histolytica

Javier-Reyna

Montaño

Garcı́a-Rivera

et al. 2019

Cellular Microbiology

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Movement and phagocytosis are clue events in colonisation and invasion of tissues by Entamoeba histolytica, the protozoan causative of human amoebiasis. During phagocytosis, EhRab proteins interact with other functional molecules, conducting them to the precise cellular site. The gene encoding EhrabB is located in the complementary chain of the DNA fragment containing Ehcp112 and Ehadh genes, which encode for the proteins of the EhCPADH complex, involved in phagocytosis. This particular genetic organisation suggests that the three corresponding proteins may be functionally related. Here, we studied the relationship of EhRabB with EhCPADH and actin during phagocytosis. First, we obtained the EhRabB 3D structure to carry out docking analysis to predict the interaction sites involved in the EhRabB protein and the EhCPADH complex contact. By confocal microscopy, transmission electron microscopy, and immunoprecipitation assays, we revealed the interaction among these proteins when they move through different vesicles formed during phagocytosis. The role of the actin cytoskeleton in this event was also confirmed using Latrunculin A to interfere with actin polymerisation. This affected the movement of EhRabB and EhCPADH, as well as the rate of phagocytosis. Mutant trophozoites, silenced in EhrabB gene, evidenced the interaction of this molecule with EhCPADH and strengthened the role of actin during erythrophagocytosis.

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Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

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EhRabB mobilises the EhCPADH complex through the actin cytoskeleton during phagocytosis of Entamoeba histolytica

Javier-Reyna

Montaño

Garcı́a-Rivera

et al. 2019

Cellular Microbiology

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“…Receptor sorting within endosome trafficking is regulated by members of the Rab family of small GTPases whose functions are membrane budding, docking, and interaction with the cytoskeleton [27, 28]. Rab4, Rab21, and Rab11 have been identified as key regulators of SST 3 trafficking [29]; however, no detailed data are available in the literature about SST 2 dynamics inside the cell.…”

Section: Introductionmentioning

confidence: 99%

Cytoskeleton Protein Filamin A Is Required for Efficient Somatostatin Receptor Type 2 Internalization and Recycling through Rab5 and Rab4 Sorting Endosomes in Tumor Somatotroph Cells

et al. 2019

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The high expression of somatostatin receptor 2 (SST₂) in growth hormone (GH)-secreting tumors represents the rationale for the clinical use of somatostatin analogs (SSAs) in acromegaly. Recently, the cytoskeletal protein Filamin A (FLNA) has emerged as key modulator of the responsiveness of GH-secreting pituitary tumors to SSAs by regulating SST₂ signaling and expression. The aim of this study was to explore FLNA involvement in SST₂ intracellular trafficking in tumor somatotroph cells. By biotinylation assay, we found that FLNA silencing abolished octreotide-mediated SST₂ internalization in rat GH3 cell line (28.0 ± 2.7 vs. 4 ± 4.3% SST₂ internalization, control versus FLNA small interfering RNAs (siRNA) cells, respectively, p < 0.001) and human GH-secreting primary cultured cells (70.3 ± 21.1 vs. 24 ± 19.2% SST₂ internalization, control versus FLNA siRNA cells, respectively, p < 0.05). In addition, confocal imaging revealed impaired SST₂ recycling to the plasma membrane in FLNA silenced GH3 cells. Coimmunoprecipitation and immunofluorescence experiments showed that FLNA, as well as β-arrestin2, is timely dependent recruited to octreotide-stimulated SST₂ receptors both in rat and human tumor somatotroph cells. Although FLNA expression knock down did not prevent the formation of β-arrestin2-SST₂ complex in GH3 cells, it significantly impaired efficient SST₂ loading into cytosolic vesicles positive for the early endocytic and recycling markers Rab5 and 4, respectively (33.7 ± 8.9% down to 25.9 ± 6.9%, p < 0.05, and 28.4 ± 7.4% down to 17.6 ± 5.7%, p < 0.01, for SST₂-Rab5 and SST₂-Rab4 colocalization, respectively, in control versus FLNA siRNA cells). Altogether these data support an important role for FLNA in the mediation of octreotide-induced SST₂ trafficking in GH-secreting pituitary tumor cells through Rab5 and 4 sorting endosomes.

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“…The formation, targeting and fusion of vesicles that transport cargos among different compartments rely on the activity of small GTPases, such as members of the Ras superfamily of monomeric G proteins (Rab) [204,205], the ADP-ribosylating factors (ARFs) [206] and members of the Rho family of GTPases [207]. Intracellular vesicles are transported along cytoskeletal components such as actin filaments or microtubules, which serve a structural role in cell shape and architecture [208,209]. Thereby, MARylation of cellular components of the intracellular transport by bARTs impairs host intracellular trafficking processes, thus sustaining the infection process [210].…”

Section: Cholera Toxin-likementioning

confidence: 99%

Targeting ADP-ribosylation as an antimicrobial strategy

Catara

Corteggio

Valente

et al. 2019

Biochemical Pharmacology

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A B S T R A C T ADP-ribosylation (ADPr) is an ancient reversible modification of cellular macromolecules controlling major biological processes as diverse as DNA damage repair, transcriptional regulation, intracellular transport, immune and stress responses, cell survival and proliferation. Furthermore, enzymatic reactions of ADPr are central in the pathogenesis of many human diseases, including infectious conditions. By providing a review of ADPr signalling in bacterial systems, we highlight the relevance of this chemical modification in the pathogenesis of human diseases depending on host-pathogen interactions. The post-antibiotic era has raised the need to find alternative approaches to antibiotic administration, as major pathogens becoming resistant to antibiotics. An in-depth understanding of ADPr reactions provides the rationale for designing novel antimicrobial strategies for treatment of infectious diseases. In addition, the understanding of mechanisms of ADPr by bacterial virulence factors offers important hints to improve our knowledge on cellular processes regulated by eukaryotic homologous enzymes, which are often involved in the pathogenesis of human diseases.T large number of worldwide spread diseases, affecting humans, insects and plants [31,[56][57][58], with a great impact on human health. In addition, infectious diseases strongly affect the world economy in terms of costs for the human health as well as food and agricultural economic losses [59]. The use of antibiotics to counteract the pathogen infections has represented the therapeutic strategy of choice in the last century, however the emergence of antibiotic resistance strains represents the major challenge of the 21st century [60][61][62]. Targeting bacterial pathogenic mechanisms by disarming pathogens of virulence factors, for instance by inhibiting the enzymatic activity of bART, represents a valid alternative intervention strategy to overcome antibiotic resistance [63][64][65][66]. In addition, because of the conservation of ADPr systems throughout the evolution, the understanding of bacterial pathogenic mechanisms may contribute to unveil novel and conserved cellular processes regulated by ADPr in high organisms [34,45,67,68]. The dysregulation of such processes can be either cause of human diseases or be target of therapeutic intervention [39,[69][70][71].Herein, we will provide a summary of bacterial ADPr systems describing their pathogenic mechanisms and highlighting the similarities with ADPr systems in mammals as well. Further, we discuss the potential of targeting ADPr for therapeutic strategies of infection diseases. ADP-ribosylation in pathophysiologyADPr was originally described in the 60s; two independent studies reported the identification of a new polymer, poly(ADP-ribose) (PAR) synthesised from NAD + in vertebrate cells [72] and, simultaneously, the finding that bacterial DTX activity from C. diphteriae is dependent on NAD + content [73]. In the following decades, research in the field has expanded the involvement of ADPr ...

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Rab and Arf proteins at the crossroad between membrane transport and cytoskeleton dynamics

Cited by 51 publications

References 225 publications

EhRabB mobilises the EhCPADH complex through the actin cytoskeleton during phagocytosis of Entamoeba histolytica

EhRabB mobilises the EhCPADH complex through the actin cytoskeleton during phagocytosis of Entamoeba histolytica

Cytoskeleton Protein Filamin A Is Required for Efficient Somatostatin Receptor Type 2 Internalization and Recycling through Rab5 and Rab4 Sorting Endosomes in Tumor Somatotroph Cells

Targeting ADP-ribosylation as an antimicrobial strategy

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