scholarly journals Symbiotic root infections in Medicago truncatula require remorin-mediated receptor stabilization in membrane nanodomains

2018 ◽  
Vol 115 (20) ◽  
pp. 5289-5294 ◽  
Author(s):  
Pengbo Liang ◽  
Thomas F. Stratil ◽  
Claudia Popp ◽  
Macarena Marín ◽  
Jessica Folgmann ◽  
...  
Keyword(s):  
Host Cell ◽  
Medicago Truncatula ◽  
Molecular Mechanisms ◽  
Cell Surface Receptor ◽  
Dependent Manner ◽  
Cell Infection ◽  
Molecular Scaffold ◽  
Rhizobial Inoculation ◽  
Surface Receptor ◽  
Functional Relevance

Plant cell infection is tightly controlled by cell surface receptor-like kinases (RLKs). Like other RLKs, the Medicago truncatula entry receptor LYK3 laterally segregates into membrane nanodomains in a stimulus-dependent manner. Although nanodomain localization arises as a generic feature of plant membrane proteins, the molecular mechanisms underlying such dynamic transitions and their functional relevance have remained poorly understood. Here we demonstrate that actin and the flotillin protein FLOT4 form the primary and indispensable core of a specific nanodomain. Infection-dependent induction of the remorin protein and secondary molecular scaffold SYMREM1 results in subsequent recruitment of ligand-activated LYK3 and its stabilization within these membrane subcompartments. Reciprocally, the majority of this LYK3 receptor pool is destabilized at the plasma membrane and undergoes rapid endocytosis in symrem1 mutants on rhizobial inoculation, resulting in premature abortion of host cell infections. These data reveal that receptor recruitment into nanodomains is indispensable for their function during host cell infection.

scholarly journals Symbiotic root infections in Medicago truncatula require remorin-mediated receptor stabilization in membrane nanodomains

2017 ◽  
Author(s):  
Pengbo Liang ◽  
Thomas F. Stratil ◽  
Claudia Popp ◽  
Macarena Marín ◽  
Jessica Folgmann ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Host Cell ◽  
Medicago Truncatula ◽  
Molecular Mechanisms ◽  
Cell Surface Receptor ◽  
Physical Interaction ◽  
Dependent Manner ◽  
Cell Infection ◽  
Molecular Scaffold ◽  
Entry Receptor

ABSTRACTPlant cell infection is tightly controlled by cell surface receptor-like kinases (RLKs) Alike other RLKs the Medicago truncatula entry receptor LYK3 laterally segregates into membrane nanodomains in a stimulus-dependent manner. Although nanodomain localization arises as a generic feature of plant membrane proteins, molecular mechanisms underlying such dynamic transitions and their functional relevance remained poorly understood. Here, we demonstrate that actin and the flotillin protein FLOT4 form the primary and indispensable core of a specific nanodomain. Infection-dependent induction of the remorin protein and secondary molecular scaffold SYMREM1 results in subsequent recruitment of ligand-activated LYK3 and its stabilization within these membrane subcompartments. Reciprocally, the majority of this LYK3 receptor pool is destabilized at the plasma membrane and undergoes rapid endocytosis in symrem1 mutants upon rhizobial inoculation resulting in premature abortion of host cell infections. These data reveal that receptor recruitment into nanodomains is indispensable for their function during host cell infection.SIGNIFICANCE STATEMENTPattern recognition receptors control the cellular entry of pathogenic as well as symbiotic microbes. While ligand-induced changes in receptor mobility at the plasma membrane and their localization in membrane nanodomains appears as a general feature, the molecular mechanism and the biological relevance of this phenomenon remained unknown. Here, we show that immobilization of the symbiotic cell entry receptor LYK3 in nanodomains requires the presence of actin and the two molecular scaffold proteins FLOT4 and SYMREM1. While FLOT4 forms the initial core structure, infection-induced expression and subsequent physical interaction of SYMREM1 with LYK3 stabilizes the activated receptors in membrane nanodomains. This recruitment prevents its stimulus-dependent endocytosis and ensures progression of the primary infection thread into root cortical cells.

Regulation of c-ret expression by retinoic acid in rat metanephros: implication in nephron mass control

1998 ◽  
Vol 275 (6) ◽  
pp. F938-F945 ◽  
Author(s):  
Evelyne Moreau ◽  
José Vilar ◽  
Martine Lelièvre-Pégorier ◽  
Claudie Merlet-Bénichou ◽  
Thierry Gilbert
Keyword(s):  
Retinoic Acid ◽  
Molecular Mechanisms ◽  
Kidney Development ◽  
Mrna Level ◽  
Cell Surface Receptor ◽  
Dependent Manner ◽  
All Trans Retinoic Acid ◽  
Surface Receptor ◽  
Dose Dependent

Vitamin A and its derivatives have been shown to promote kidney development in vitro in a dose-dependent fashion. To address the molecular mechanisms by which all- trans-retinoic acid (RA) may regulate the nephron mass, rat kidneys were removed on embryonic day 14( E14) and grown in organ culture under standard or RA-stimulated conditions. By using RT-PCR, we studied the expression of the glial cell line-derived neurotrophic factor (GDNF), its cell surface receptor-α (GDNFR-α), and the receptor tyrosine kinase c-ret, known to play a major role in renal organogenesis. Expression of GDNF and GDNFR-α transcripts was high at the time of explantation and remained unaffected in culture with or without RA. In contrast, c-ret mRNA level, which was low in E14 metanephros and dropped rapidly in vitro, was increased by RA in a dose-dependent manner. The same is true at the protein level. Exogenous GDNF barely promotes additional nephron formation in vitro. Thus the present data establish c-ret as a key target of retinoids during kidney organogenesis.

scholarly journals Dectin-1-Mediated Production of Pro-Inflammatory Cytokines Induced by Yeast β-Glucans in Bovine Monocytes

2021 ◽  
Vol 12 ◽  
Author(s):  
Ana R. V. Pedro ◽  
Tânia Lima ◽  
Ricardo Fróis-Martins ◽  
Bárbara Leal ◽  
Isabel C. Ramos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Surface ◽  
Inflammatory Cytokines ◽  
Surface Expression ◽  
Cell Surface Receptor ◽  
Dependent Manner ◽  
Feed Supplements ◽  
Surface Receptor ◽  
Dose Dependent ◽  
Pro Inflammatory Cytokines

Yeast-derived products containing β-glucans have long been used as feed supplements in domesticated animals in an attempt to increase immunity. β-glucans are mainly recognized by the cell surface receptor CLEC7A, also designated Dectin-1. Although the immune mechanisms elicited through Dectin-1 activation have been studied in detail in mice and humans, they are poorly understood in other species. Here, we evaluated the response of bovine monocytes to soluble and particulate purified β-glucans, and also to Zymosan. Our results show that particulate, but not soluble β-glucans, can upregulate the surface expression of costimulatory molecules CD80 and CD86 on bovine monocytes. In addition, stimulated cells increased production of IL-8 and of TNF, IL1B, and IL6 mRNA expression, in a dose-dependent manner, which correlated positively with CLEC7A gene expression. Production of IL-8 and TNF expression decreased significantly after CLEC7A knockdown using two different pairs of siRNAs. Overall, we demonstrated here that bovine monocytes respond to particulate β-glucans, through Dectin-1, by increasing the expression of pro-inflammatory cytokines. Our data support further studies in cattle on the induction of trained immunity using dietary β-glucans.

scholarly journals Leptospiral Endostatin-Like Protein A Is a Bacterial Cell Surface Receptor for Human Plasminogen

2010 ◽  
Vol 78 (5) ◽  
pp. 2053-2059 ◽  
Author(s):  
Ashutosh Verma ◽  
Catherine A. Brissette ◽  
Amy A. Bowman ◽  
Samir T. Shah ◽  
Peter F. Zipfel ◽  
...  
Keyword(s):  
Binding Sites ◽  
Protein A ◽  
Aminocaproic Acid ◽  
Factor H ◽  
Cell Surface Receptor ◽  
Dependent Manner ◽  
Public Health Importance ◽  
Amino Terminal ◽  
Surface Receptor ◽  
Human Plasminogen

ABSTRACT The spirochete Leptospira interrogans is a highly invasive pathogen of worldwide public health importance. Studies from our laboratories and another have demonstrated that L. interrogans can acquire host plasminogen on its surface. Exogenous plasminogen activators can then convert bound plasminogen into the functionally active protease plasmin. In this study, we extend upon those observations and report that leptospiral endostatin-like protein A (LenA) binds human plasminogen in a dose-dependent manner. LenA-plasminogen interactions were significantly inhibited by the lysine analog ξ-aminocaproic acid, suggesting that the lysine-binding sites on the amino-terminal kringle portion of the plasminogen molecule play a role in the binding. Previous studies have shown that LenA also binds complement regulator factor H and the extracellular matrix component laminin. Plasminogen competed with both factor H and laminin for binding to LenA, which suggests overlapping ligand-binding sites on the bacterial receptor. Finally, LenA-bound plasminogen could be converted to plasmin, which in turn degraded fibrinogen, suggesting that acquisition of host-derived plasmin by LenA may aid bacterial dissemination throughout host tissues.

Molecular mechanisms underlying the sensing of extracellular Ca2+ by parathyroid and kidney cells

1995 ◽  
Vol 132 (5) ◽  
pp. 523-531 ◽  
Author(s):  
Edward M Brown ◽  
Martin Pollak ◽  
Steven C Hebert
Keyword(s):  
G Protein ◽  
Molecular Mechanisms ◽  
Ion Homeostasis ◽  
Indirect Evidence ◽  
Second Messenger ◽  
Cell Surface Receptor ◽  
Expression Cloning ◽  
Kidney Cells ◽  
Dependent Manner ◽  
Inherited Disorders

Brown EM, Pollak M, Hebert SC. Molecular mechanisms underlying the sensing of extracellular Ca2+ by parathyroid and kidney cells. Eur J Endocrinol 1995;132:523–31. ISSN 0804–4643 Mineral ion homeostasis in mammalian species is maintained by a complex mechanism comprising sensors of the extracellular calcium concentration (Ca02+) (i.e. parathyroid cells) as well as effectors that modify their translocation of mineral ions into and out of the extracellular fluid (e.g. kidney) in response to calciotropic hormones. Indirect evidence accumulated over the past decade suggested that parathyroid cells sense Ca02+ through a cell surface receptor coupled to intracellular second messenger systems via one or more guanine nucleotide regulatory (G) proteins. More recently, Brown et al. employed expression cloning in Xenopus laevis oocytes to isolate a cDNA encoding a Ca02+-sensing receptor from bovine parathyroid. The expressed receptor activates phospholipase C in a G-protein dependent manner and shows pharmacological properties almost identical to those of the native parathyroid receptor. Agonists for the receptor include not only divalent cations (e.g. Ca2+ and Mg2+) but also trivalent cations and even organic polycations such as neomycin. The deduced amino acid sequence of the cloned receptor confirms that it is a member of the superfamily of G-protein-coupled receptors. Receptor transcripts are present in parathyroid as well as in kidney, thyroid and brain. Therefore, this receptor may mediate the sensing of Ca02+ not only by parathyroid cells but also by other tissues directly regulated by Ca02+ (e.g. the thyroidal C cells and certain kidney cells) as well as those not currently known to be involved in calcium homeostasis (viz. in the brain). Further evidence for the physiological relevance of the receptor comes from the discovery that mutations in the human homolog of the Ca02+-sensing receptor gene cause three inherited disorders of mineral ion homeostasis. Familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism are the clinical expression of inactivating mutations of the receptor when present in the heterozygous and homozygous state, respectively. An autosomal dominant form of hypocalcemia, on the other hand, results from an activating mutation of the receptor. Thus, this Ca02+-sensing receptor permits Ca02+ to act, in effect, as an extracellular first messenger in addition to its more widely recognized role as an intracellular second messenger. Edward M Brown, Endocrine–Hypertension Division, Brigham and Women's Hospital, 221 Longwood Ave, Boston, MA02115, USA

scholarly journals Characterization of Sec-Translocon-Dependent Extracytoplasmic Proteins of Rickettsia typhi

2008 ◽  
Vol 190 (18) ◽  
pp. 6234-6242 ◽  
Author(s):  
Nicole C. Ammerman ◽  
M. Sayeedur Rahman ◽  
Abdu F. Azad
Keyword(s):  
Host Cell ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Host Cells ◽  
Transcriptional Analysis ◽  
Mammalian Host ◽  
Signal Peptides ◽  
Cell Infection ◽  
Rickettsia Typhi ◽  
Sec Translocon

ABSTRACT As obligate intracellular, vector-borne bacteria, rickettsiae must adapt to both mammalian and arthropod host cell environments. Deciphering the molecular mechanisms of the interactions between rickettsiae and their host cells has largely been hindered by the genetic intractability of these organisms; however, research in other gram-negative pathogens has demonstrated that many bacterial determinants of attachment, entry, and pathogenesis are extracytoplasmic proteins. The annotations of several rickettsial genomes indicate the presence of homologs of the Sec translocon, the major route for bacterial protein secretion from the cytoplasm. For Rickettsia typhi, the etiologic agent of murine typhus, homologs of the Sec-translocon-associated proteins LepB, SecA, and LspA have been functionally characterized; therefore, the R. typhi Sec apparatus represents a mechanism for the secretion of rickettsial proteins, including virulence factors, into the extracytoplasmic environment. Our objective was to characterize such Sec-dependent R. typhi proteins in the context of a mammalian host cell infection. By using the web-based programs LipoP, SignalP, and Phobius, a total of 191 R. typhi proteins were predicted to contain signal peptides targeting them to the Sec translocon. Of these putative signal peptides, 102 were tested in an Escherichia coli-based alkaline phosphatase (PhoA) gene fusion system. Eighty-four of these candidates exhibited signal peptide activity in E. coli, and transcriptional analysis indicated that at least 54 of the R. typhi extracytoplasmic proteins undergo active gene expression during infections of HeLa cells. This work highlights a number of interesting proteins possibly involved in rickettsial growth and virulence in mammalian cells.

scholarly journals Identification of the Cellular Receptor of Clostridium spiroforme Toxin

2012 ◽  
Vol 80 (4) ◽  
pp. 1418-1423 ◽  
Author(s):  
Panagiotis Papatheodorou ◽  
Claudia Wilczek ◽  
Thilo Nölke ◽  
Gregor Guttenberg ◽  
Daniel Hornuss ◽  
...  
Keyword(s):  
Host Cell ◽  
Cell Receptor ◽  
Cell Surface Receptor ◽  
Target Cells ◽  
Content Type ◽  
Recombinant Production ◽  
Host Cell Receptor ◽  
Surface Receptor ◽  
Microscopic Studies ◽  
Host Cell Surface

ABSTRACTClostridium spiroformeproduces the binary actin-ADP-ribosylating toxin CST (C. spiroformetoxin), which has been proposed to be responsible for diarrhea, enterocolitis, and eventually death, especially in rabbits. Here we report on the recombinant production of the enzyme component (CSTa) and the binding component (CSTb) ofC. spiroformetoxin inBacillus megaterium. By using the recombinant toxin components, we show that CST enters target cells via the lipolysis-stimulated lipoprotein receptor (LSR), which has been recently identified as the host cell receptor of the binary toxinsClostridium difficiletransferase (CDT) andClostridium perfringensiota toxin. Microscopic studies revealed that CST, but not the relatedClostridium botulinumC2 toxin, colocalized with LSR during toxin uptake and traffic to endosomal compartments. Our findings indicate that CST shares LSR withC. difficileCDT andC. perfringensiota toxin as a host cell surface receptor.

scholarly journals Thyroid Hormone and P-Glycoprotein in Tumor Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Paul J. Davis ◽  
Sandra Incerpi ◽  
Hung-Yun Lin ◽  
Heng-Yuan Tang ◽  
Thangirala Sudha ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Efflux Pump ◽  
Inhibitory Effect ◽  
Chemotherapeutic Agents ◽  
Cell Surface Receptor ◽  
P Glycoprotein ◽  
Surface Receptor

P-glycoprotein (P-gp; multidrug resistance pump 1, MDR1; ABCB1) is a plasma membrane efflux pump that when activated in cancer cells exports chemotherapeutic agents. Transcription of the P-gp gene (MDR1) and activity of the P-gp protein are known to be affected by thyroid hormone. A cell surface receptor for thyroid hormone on integrinαvβ3 also binds tetraiodothyroacetic acid (tetrac), a derivative of L-thyroxine (T4) that blocks nongenomic actions of T4and of 3,5,3′-triiodo-L-thyronine (T3) atαvβ3. Covalently bound to a nanoparticle, tetrac as nanotetrac acts at the integrin to increase intracellular residence time of chemotherapeutic agents such as doxorubicin and etoposide that are substrates of P-gp. This action chemosensitizes cancer cells. In this review, we examine possible molecular mechanisms for the inhibitory effect of nanotetrac on P-gp activity. Mechanisms for consideration include cancer cell acidification via action of tetrac/nanotetrac on the Na+/H+exchanger (NHE1) and hormone analogue effects on calmodulin-dependent processes and on interactions of P-gp with epidermal growth factor (EGF) and osteopontin (OPN), apparently viaαvβ3. Intracellular acidification and decreased H+efflux induced by tetrac/nanotetrac via NHE1 is the most attractive explanation for the actions on P-gp and consequent increase in cancer cell retention of chemotherapeutic agent-ligands of MDR1 protein.

scholarly journals Coxiella burnetiiblocks intracellular IL-17 signaling in macrophages

2018 ◽  
Author(s):  
Tatiana M. Clemente ◽  
Minal Mulye ◽  
Anna V. Justis ◽  
Srinivas Nallandhighal ◽  
Tuan M. Tran ◽  
...  
Keyword(s):  
Host Cell ◽  
Q Fever ◽  
Protective Role ◽  
Effector Proteins ◽  
Antimicrobial Protein ◽  
Dependent Manner ◽  
Cell Infection ◽  
Protein Levels ◽  
Host Cytoplasm ◽  
Infected Cells

AbstractCoxiella burnetiiis an obligate intracellular bacterium and the etiological agent of Q fever. Successful host cell infection requires theCoxiellaType IVB Secretion System (T4BSS), which translocates bacterial effector proteins across the vacuole membrane into the host cytoplasm, where they manipulate a variety of cell processes. To identify host cell targets ofCoxiellaT4BSS effector proteins, we determined the transcriptome of murine alveolar macrophages infected with aCoxiellaT4BSS effector mutant. We identified a set of inflammatory genes that are significantly upregulated in T4BSS mutant-infected cells compared to mock-infected cells or cells infected with wild type (WT) bacteria, suggestingCoxiellaT4BSS effector proteins downregulate expression of these genes. In addition, the IL-17 signaling pathway was identified as one of the top pathways affected by the bacteria. While previous studies demonstrated that IL-17 plays a protective role against several pathogens, the role of IL-17 duringCoxiellainfection is unknown. We found that IL-17 kills intracellularCoxiellain a dose-dependent manner, with the T4BSS mutant exhibiting significantly more sensitivity to IL-17 than WT bacteria. In addition, quantitative PCR confirmed increased expression of IL-17 downstream signaling genes in T4BSS mutant-infected cells compared to WT or mock-infected cells, including the pro-inflammatory cytokinesI11a, Il1bandTnfa, the chemokinesCxcl2andCcl5, and the antimicrobial proteinLcn2. We further confirmed that theCoxiellaT4BSS downregulates macrophage CXCL2/MIP-2 and CCL5/RANTES protein levels following IL-17 stimulation. Together, these data suggest thatCoxielladownregulates IL-17 signaling in a T4BSS-dependent manner in order to escape the macrophage immune response.

scholarly journals Molecular Mechanisms of Brassinosteroid-Mediated Responses to Changing Environments in Arabidopsis

2020 ◽  
Vol 21 (8) ◽  
pp. 2737 ◽  
Author(s):  
Minghui Lv ◽  
Jia Li
Keyword(s):  
Molecular Mechanisms ◽  
Cell Surface Receptor ◽  
Signal Molecules ◽  
Environmental Cues ◽  
Receptor Complex ◽  
Changing Environments ◽  
Plant Adaptations ◽  
Surface Receptor ◽  
Growth Promoting ◽  
External Stimuli

Plant adaptations to changing environments rely on integrating external stimuli into internal responses. Brassinosteroids (BRs), a group of growth-promoting phytohormones, have been reported to act as signal molecules mediating these processes. BRs are perceived by cell surface receptor complex including receptor BRI1 and coreceptor BAK1, which subsequently triggers a signaling cascade that leads to inhibition of BIN2 and activation of BES1/BZR1 transcription factors. BES1/BZR1 can directly regulate the expression of thousands of downstream responsive genes. Recent studies in the model plant Arabidopsis demonstrated that BR biosynthesis and signal transduction, especially the regulatory components BIN2 and BES1/BZR1, are finely tuned by various environmental cues. Here, we summarize these research updates and give a comprehensive review of how BR biosynthesis and signaling are modulated by changing environments and how these changes regulate plant adaptive growth or stress tolerance.

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