Small GTPases and Brucella entry into the endoplasmic reticulum

2012 ◽  
Vol 40 (6) ◽  
pp. 1348-1352 ◽  
Author(s):  
Xavier de Bolle ◽  
Jean-Jacques Letesson ◽  
Jean-Pierre Gorvel
Keyword(s):  
Endoplasmic Reticulum ◽  
Pathogenic Bacteria ◽  
Wild Type Strain ◽  
Specific Interaction ◽  
Small Gtpases ◽  
Small Gtpase ◽  
Endocytic Pathway ◽  
Host Cells ◽  
Kinetics Of ◽  
Membrane Reservoir

A key determinant for intracellular pathogenic bacteria to ensure their virulence within host cells is their ability to bypass the endocytic pathway and to reach a safe niche of replication. In the case of Brucella, the bacterium targets the ER (endoplasmic reticulum) to create a replicating niche called the BCV (Brucella-containing vacuole). The ER is a suitable strategic place for pathogenic Brucella. Indeed, bacteria can be hidden from host cell defences to persist within the host, and they can take advantage of the membrane reservoir delivered by the ER to replicate. Interaction with the ER leads to the presence on the BCV of the GAPDH (glyceraldehyde-3-phosphate dehydrogenase) and the small GTPase Rab2 known to be located on secretory vesicles that traffic between the ER and the Golgi apparatus. GAPDH and the small GTPase Rab2 controls Brucella replication at late times post-infection. A specific interaction between the human small GTPase Rab2 and a Brucella spp. protein named RicA was identified. Altered kinetics of intracellular trafficking and faster proliferation of the Brucella abortus ΔricA mutant was observed compared with the wild-type strain. RicA is the first reported effector with a proposed function for B. abortus.

scholarly journals Clathrin- and caveolin-1–independent endocytosis

2005 ◽  
Vol 168 (3) ◽  
pp. 477-488 ◽  
Author(s):  
Eva-Maria Damm ◽  
Lucas Pelkmans ◽  
Jürgen Kartenbeck ◽  
Anna Mezzacasa ◽  
Teymuras Kurzchalia ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Knockout Mouse ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Endocytic Pathway ◽  
Host Cells ◽  
Human Hepatoma ◽  
Wild Type ◽  
Embryonic Fibroblasts ◽  
Caveolin 1

Simian Virus 40 (SV40) has been shown to enter host cells by caveolar endocytosis followed by transport via caveosomes to the endoplasmic reticulum (ER). Using a caveolin-1 (cav-1)–deficient cell line (human hepatoma 7) and embryonic fibroblasts from a cav-1 knockout mouse, we found that in the absence of caveolae, but also in wild-type embryonic fibroblasts, the virus exploits an alternative, cav-1–independent pathway. Internalization was rapid (t1/2 = 20 min) and cholesterol and tyrosine kinase dependent but independent of clathrin, dynamin II, and ARF6. The viruses were internalized in small, tight-fitting vesicles and transported to membrane-bounded, pH-neutral organelles similar to caveosomes but devoid of cav-1 and -2. The viruses were next transferred by microtubule-dependent vesicular transport to the ER, a step that was required for infectivity. Our results revealed the existence of a virus-activated endocytic pathway from the plasma membrane to the ER that involves neither clathrin nor caveolae and that can be activated also in the presence of cav-1.

scholarly journals Modulation of host microtubule dynamics by pathogenic bacteria

2012 ◽  
Vol 3 (6) ◽  
pp. 571-580 ◽  
Author(s):  
Girish K. Radhakrishnan ◽  
Gary A. Splitter
Keyword(s):  
Pathogenic Bacteria ◽  
Bacterial Pathogens ◽  
Small Gtpases ◽  
Microtubule Dynamics ◽  
Effector Proteins ◽  
Host Cells ◽  
Microbial Pathogens ◽  
Survival Strategies ◽  
Future Research ◽  
Bacterial Effectors

AbstractThe eukaryotic cytoskeleton is a vulnerable target of many microbial pathogens during the course of infection. Rearrangements of host cytoskeleton benefit microbes in various stages of their infection cycle such as invasion, motility, and persistence. Bacterial pathogens deliver a number of effector proteins into host cells for modulating the dynamics of actin and microtubule cytoskeleton. Alteration of the actin cytoskeleton is generally achieved by bacterial effectors that target the small GTPases of the host. Modulation of microtubule dynamics involves direct interaction of effector proteins with the subunits of microtubules or recruiting cellular proteins that affect microtubule dynamics. This review will discuss effector proteins from animal and human bacterial pathogens that either destabilize or stabilize host microtubules to advance the infectious process. A compilation of these research findings will provide an overview of known and unknown strategies used by various bacterial effectors to modulate the host microtubule dynamics. The present review will undoubtedly help direct future research to determine the mechanisms of action of many bacterial effector proteins and contribute to understanding the survival strategies of diverse adherent and invasive bacterial pathogens.

Clinical, Cellular, and Molecular Aspects of Cancer Invasion

2003 ◽  
Vol 83 (2) ◽  
pp. 337-376 ◽  
Author(s):  
Marc Mareel ◽  
Ancy Leroy
Keyword(s):  
Cancer Cells ◽  
Cross Talk ◽  
Tyrosine Kinases ◽  
Molecular Mechanisms ◽  
Platelet Activating Factor ◽  
Tumor Development ◽  
Genetic Alterations ◽  
Small Gtpases ◽  
Small Gtpase ◽  
Host Cells

Invasion causes cancer malignancy. We review recent data about cellular and molecular mechanisms of invasion, focusing on cross-talk between the invaders and the host. Cancer disturbs these cellular activities that maintain multicellular organisms, namely, growth, differentiation, apoptosis, and tissue integrity. Multiple alterations in the genome of cancer cells underlie tumor development. These genetic alterations occur in varying orders; many of them concomitantly influence invasion as well as the other cancer-related cellular activities. Examples discussed are genes encoding elements of the cadherin/catenin complex, the nonreceptor tyrosine kinase Src, the receptor tyrosine kinases c-Met and FGFR, the small GTPase Ras, and the dual phosphatase PTEN. In microorganisms, invasion genes belong to the class of virulence genes. There are numerous clinical and experimental observations showing that invasion results from the cross-talk between cancer cells and host cells, comprising myofibroblasts, endothelial cells, and leukocytes, all of which are themselves invasive. In bone metastases, host osteoclasts serve as targets for therapy. The molecular analysis of invasion-associated cellular activities, namely, homotypic and heterotypic cell-cell adhesion, cell-matrix interactions and ectopic survival, migration, and proteolysis, reveal branching signal transduction pathways with extensive networks between individual pathways. Cellular responses to invasion-stimulatory molecules such as scatter factor, chemokines, leptin, trefoil factors, and bile acids or inhibitory factors such as platelet activating factor and thrombin depend on activation of trimeric G proteins, phosphoinositide 3-kinase, and the Rac and Rho family of small GTPases. The role of proteolysis in invasion is not limited to breakdown of extracellular matrix but also causes cleavage of proinvasive fragments from cell surface glycoproteins.

Early endocytic Rabs: functional prediction to functional characterization.

2005 ◽  
Vol 72 ◽  
pp. 99-108 ◽  
Author(s):  
Jeremy C Simpson ◽  
Arwyn T Jones
Keyword(s):  
Membrane Trafficking ◽  
Functional Characterization ◽  
Specific Interaction ◽  
Small Gtpases ◽  
Endocytic Pathway ◽  
Functional Prediction ◽  
Final Destination ◽  
Similarities And Differences ◽  
And Function ◽  
Endocytic Pathways

Endocytic pathways are highly dynamic gateways for molecules to enter cells. Functionality and specificity is in part controlled by a number of small GTPases called Rabs. In defined cellular locations, Rabs mediate multiple functions in membrane trafficking via their specific interaction with organelle membranes and a host of affector and effector molecules. On endocytic pathways, Rabs have been shown to control the formation of vesicles on the plasma membrane and the downstream delivery of internalized molecules to a number of cellular locations. As numerous Rabs are located to endocytic pathways, an internalized molecule may traverse a number of Rab specific substations or subdomains en route to its final destination. Rabs 5, 21 and 22 have all been localized to the early endocytic pathway and have been shown to share a number of characteristics to merit their segregation into a single functional endocytic group. In this review, we compare experiments that describe similarities and differences in endosome morphology and function that is mediated by their expression in cells.

scholarly journals Rab39a and Rab39b Display Different Intracellular Distribution and Function in Sphingolipids and Phospholipids Transport

2019 ◽  
Vol 20 (7) ◽  
pp. 1688 ◽  
Author(s):  
Julián Gambarte Tudela ◽  
Julio Buonfigli ◽  
Agustín Luján ◽  
Mariano Alonso Bivou ◽  
Ignacio Cebrián ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Biology ◽  
Small Gtpases ◽  
Intracellular Distribution ◽  
Endocytic Pathway ◽  
Lipid Transport ◽  
Amino Acid Sequence Similarity ◽  
Multivesicular Bodies ◽  
Rab Gtpases ◽  
And Function

Rab GTPases define the identity and destiny of vesicles. Some of these small GTPases present isoforms that are expressed differentially along developmental stages or in a tissue-specific manner, hence comparative analysis is difficult to achieve. Here, we describe the intracellular distribution and function in lipid transport of the poorly characterized Rab39 isoforms using typical cell biology experimental tools and new ones developed in our laboratory. We show that, despite their amino acid sequence similarity, Rab39a and Rab39b display non-overlapping intracellular distribution. Rab39a localizes in the late endocytic pathway, mainly at multivesicular bodies. In contrast, Rab39b distributes in the secretory network, at the endoplasmic reticulum/cis-Golgi interface. Therefore, Rab39a controls trafficking of lipids (sphingomyelin and phospholipids) segregated at multivesicular bodies, whereas Rab39b transports sphingolipids biosynthesized at the endoplasmic reticulum-Golgi factory. Interestingly, lyso bis-phosphatidic acid is exclusively transported by Rab39a, indicating that both isoforms do not exert identical functions in lipid transport. Conveniently, the requirement of eukaryotic lipids by the intracellular pathogen Chlamydia trachomatis rendered useful for dissecting and distinguishing Rab39a- and Rab39b-controlled trafficking pathways. Our findings provide comparative insights about the different subcellular distribution and function in lipid transport of the two Rab39 isoforms.

scholarly journals Rab18 regulates focal adhesion dynamics by interacting with kinectin-1 at the endoplasmic reticulum

2020 ◽  
Vol 219 (7) ◽  
Author(s):  
Noemi Antonella Guadagno ◽  
Azzurra Margiotta ◽  
Synne Arstad Bjørnestad ◽  
Linda Hofstad Haugen ◽  
Ingrid Kjos ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Focal Adhesion ◽  
Focal Adhesions ◽  
Molecular Switches ◽  
Underlying Mechanism ◽  
Small Gtpases ◽  
Small Gtpase ◽  
Canonical Function ◽  
Dependent Transport

The members of the Rab family of small GTPases are molecular switches that regulate distinct steps in different membrane traffic pathways. In addition to this canonical function, Rabs can play a role in other processes, such as cell adhesion and motility. Here, we reveal the role of the small GTPase Rab18 as a positive regulator of directional migration in chemotaxis, and the underlying mechanism. We show that knockdown of Rab18 reduces the size of focal adhesions (FAs) and influences their dynamics. Furthermore, we found that Rab18, by directly interacting with the endoplasmic reticulum (ER)-resident protein kinectin-1, controls the anterograde kinesin-1–dependent transport of the ER required for the maturation of nascent FAs and protrusion orientation toward a chemoattractant. Altogether, our data support a model in which Rab18 regulates kinectin-1 transport toward the cell surface to form ER–FA contacts, thus promoting FA growth and cell migration during chemotaxis.

scholarly journals Role of three rab5-like GTPases, Ypt51p, Ypt52p, and Ypt53p, in the endocytic and vacuolar protein sorting pathways of yeast.

1994 ◽  
Vol 125 (2) ◽  
pp. 283-298 ◽  
Author(s):  
B Singer-Krüger ◽  
H Stenmark ◽  
A Düsterhöft ◽  
P Philippsen ◽  
J S Yoo ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Lucifer Yellow ◽  
Protein Sorting ◽  
Personal Communication ◽  
Small Gtpases ◽  
Small Gtpase ◽  
Endocytic Pathway ◽  
Phenotypic Characterization ◽  
Vacuolar Protein Sorting ◽  
Vacuolar Protein

The small GTPase rab5 has been shown to represent a key regulator in the endocytic pathway of mammalian cells. Using a PCR approach to identify rab5 homologs in Saccharomyces cerevisiae, two genes encoding proteins with 54 and 52% identity to rab5, YPT51 and YPT53 have been identified. Sequencing of the yeast chromosome XI has revealed a third rab5-like gene, YPT52, whose protein product exhibits a similar identity to rab5 and the other two YPT gene products. In addition to the high degree of identity/homology shared between rab5 and Ypt51p, Ypt52p, and Ypt53p, evidence for functional homology between the mammalian and yeast proteins is provided by phenotypic characterization of single, double, and triple deletion mutants. Endocytic delivery to the vacuole of two markers, lucifer yellow CH (LY) and alpha-factor, was inhibited in delta ypt51 mutants and aggravated in the double ypt51ypt52 and triple ypt51ypt52ypt53 mutants, suggesting a requirement for these small GTPases in endocytic membrane traffic. In addition to these defects, the here described ypt mutants displayed a number of other phenotypes reminiscent of some vacuolar protein sorting (vps) mutants, including a differential delay in growth and vacuolar protein maturation, partial missorting of a soluble vacuolar hydrolase, and alterations in vacuole acidification and morphology. In fact, vps21 represents a mutant allele of YPT51 (Emr, S., personal communication). Altogether, these data suggest that Ypt51p, Ypt52p, and Ypt53p are required for transport in the endocytic pathway and for correct sorting of vacuolar hydrolases suggesting a possible intersection of the endocytic with the vacuolar sorting pathway.

scholarly journals Effects of ß-glucans on the immune system

Medicina ◽  
2007 ◽  
Vol 43 (8) ◽  
pp. 597 ◽  
Author(s):  
Dalia Akramienė ◽  
Anatolijus Kondrotas ◽  
Janina Didžiapetrienė ◽  
Egidijus Kėvelaitis
Keyword(s):  
Tumor Cells ◽  
Complement System ◽  
Pathogenic Bacteria ◽  
Killer Cell ◽  
Specific Interaction ◽  
Immune Defense ◽  
Biologically Active ◽  
Host Cells ◽  
Complement Receptor ◽  
Complement Receptor 3

ß-Glucans are naturally occurring polysaccharides. These glucose polymers are constituents of the cell wall of certain pathogenic bacteria and fungi. The healing and immunostimulating properties of mushrooms have been known for thousands of years in the Eastern countries. These mushrooms contain biologically active polysaccharides that mostly belong to group of ß-glucans. These substances increase host immune defense by activating complement system, enhancing macrophages and natural killer cell function. The induction of cellular responses by mushroom and other ß-glucans is likely to involve their specific interaction with several cell surface receptors, as complement receptor 3 (CR3; CD11b/CD18), lactosylceramide, selected scavenger receptors, and dectin-1 (ßGR). ß-Glucans also show anticarcinogenic activity. They can prevent oncogenesis due to the protective effect against potent genotoxic carcinogens. As immunostimulating agent, which acts through the activation of macrophages and NK cell cytotoxicity, ß-glucan can inhibit tumor growth in promotion stage too. Antiangiogenesis can be one of the pathways through which ß-glucans can reduce tumor proliferation, prevent tumor metastasis. ß-Glucan as adjuvant to cancer chemotherapy and radiotherapy demonstrated the positive role in the restoration of hematopiesis following by bone marrow injury. Immunotherapy using monoclonal antibodies is a novel strategy of cancer treatment. These antibodies activate complement system and opsonize tumor cells with iC3b fragment. In contrast to microorganisms, tumor cells, as well as other host cells, lack ß-glucan as a surface component and cannot trigger complement receptor 3-dependent cellular cytotoxicity and initiate tumor-killing activity. This mechanism could be induced in the presence of ß-glucans.

scholarly journals A Retromerlike Complex Is a Novel Rab7 Effector That Is Involved in the Transport of the Virulence Factor Cysteine Protease in the Enteric Protozoan ParasiteEntamoeba histolytica

2005 ◽  
Vol 16 (11) ◽  
pp. 5294-5303 ◽  
Author(s):  
Kumiko Nakada-Tsukui ◽  
Yumiko Saito-Nakano ◽  
Vahab Ali ◽  
Tomoyoshi Nozaki
Keyword(s):  
Cysteine Protease ◽  
Specific Interaction ◽  
Protozoan Parasite ◽  
Retrograde Transport ◽  
Small Gtpase ◽  
Host Cells ◽  
Lysosomal Cysteine Protease ◽  
Direct Binding ◽  
Intracellular Sorting ◽  
Enteric Protozoan

Vesicular trafficking plays an important role in a virulence mechanism of the enteric protozoan parasite Entamoeba histolytica as secreted and lysosomal cysteine protease (CP) contributes to both cytolysis of tissues and degradation of internalized host cells. Despite the primary importance of intracellular sorting in pathogenesis, the molecular mechanism of CP trafficking remains largely unknown. In this report we demonstrate that transport of CP is regulated through a specific interaction of Rab7A small GTPase (EhRab7A) with the retromerlike complex. The amoebic retromerlike complex composed of Vps26, Vps29, and Vps35 was identified as EhRab7A-binding proteins. The amoebic retromerlike complex specifically bound to GTP-EhRab7A, but not GDP-EhRab7A through the direct binding via the carboxy terminus of EhVps26. In erythrophagocytosis the retromerlike complex was recruited to prephagosomal vacuoles, the unique preparatory vacuole of digestive enzymes, and later to phagosomes. This dynamism was indistinguishable from that of EhRab7A, and consistent with the premise that the retromerlike complex is involved in the retrograde transport of putative hydrolase receptor(s) from preparatory vacuoles and phagosomes to the Golgi apparatus. EhRab7A overexpression caused enlargement of lysosomes and decrease of the cellular CP activity. The reduced CP activity was restored by the coexpression of EhVps26, implying that the EhRab7A-mediated transport of CP to phagosomes is regulated by the retromerlike complex.

Basic Biology of Trypanosoma Cruzi

2020 ◽  
Vol 26 ◽  
Author(s):  
Aline Araujo Zuma ◽  
Emile dos Santos Barrias ◽  
Wanderley de Souza
Keyword(s):  
Trypanosoma Cruzi ◽  
Trypanosoma Brucei ◽  
Cell Biology ◽  
Structural Organization ◽  
Developmental Stages ◽  
Endocytic Pathway ◽  
Host Cells ◽  
Cellular Organization ◽  
Basic Biology ◽  
Comparative Information

Abstract:: The present review addresses basic aspects of the biology of the pathogenic protozoa Trypanosoma cruzi and some comparative information with Trypanosoma brucei. Like eukaryotic cells, their cellular organization is similar to that of mammalian hosts. However, these parasites present structural particularities. That is why the following topics are emphasized in this paper: developmental stages of the life cycle in the vertebrate and invertebrate hosts; the cytoskeleton of the protozoa, especially the sub-pellicular microtubules; the flagellum and its attachment to the protozoan body through specialized junctions; the kinetoplast-mitochondrion complex, including its structural organization and DNA replication; the glycosome and its role in the metabolism of the cell; the acidocalcisome, describing its morphology, biochemistry, and functional role; the cytostome and the endocytic pathway; the organization of the endoplasmic reticulum and Golgi complex; the nucleus, describing its structural organization during interphase and division; and the process of interaction of the parasite with host cells. The unique characteristics of these structures also make them interesting chemotherapeutic targets. Therefore, further understanding of cell biology aspects contributes to the development of drugs for chemotherapy.

Sign in / Sign up

Export Citation Format

Share Document