scholarly journals Phosphatidylinositol 4,5-bisphosphate regulates cilium transition zone maturation in Drosophila melanogaster

2018 ◽  
Author(s):  
Alind Gupta ◽  
Lacramioara Fabian ◽  
Julie A. Brill
Keyword(s):  
Drosophila Melanogaster ◽  
Plasma Membrane ◽  
Transition Zone ◽  
Genetic Disorders ◽  
Ectopic Expression ◽  
Membrane Lipid ◽  
Type I ◽  
Male Germline ◽  
Membrane Tethering ◽  
And Function

AbstractCilia are cellular antennae that are essential for human development and physiology. A large number of genetic disorders linked to cilium dysfunction are associated with proteins that localize to the ciliary transition zone (TZ), a structure at the base of cilia that regulates trafficking in and out of the cilium. Despite substantial effort to identify TZ proteins and their roles in cilium assembly and function, processes underlying maturation of TZs are not well understood. Here, we report a role for the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) in TZ maturation in the Drosophila melanogaster male germline. We show that reduction of cellular PIP2 levels by ectopic expression of a phosphoinositide phosphatase or mutation of the type I phosphatidylinositol phosphate kinase Skittles induces formation of longer than normal TZs. These hyperelongated TZs exhibit functional defects, including loss of plasma membrane tethering. We also report that the onion rings (onr) allele of Drosophila exo84 decouples TZ hyperelongation from loss of cilium-plasma membrane tethering. Our results reveal a requirement for PIP2 in supporting ciliogenesis by promoting proper TZ maturation.Brief summary statementThe authors show that the membrane phospholipid PIP2, and the kinase that produces PIP2 called Skittles, are needed for normal ciliary transition zone morphology and function in the Drosophila male germline.

scholarly journals Impact of Membrane Lipids on UapA and AzgA Transporter Subcellular Localization and Activity in Aspergillus nidulans

2021 ◽  
Vol 7 (7) ◽  
pp. 514
Author(s):  
Mariangela Dionysopoulou ◽  
George Diallinas
Keyword(s):  
Plasma Membrane ◽  
Subcellular Localization ◽  
Aspergillus Nidulans ◽  
Membrane Lipids ◽  
Membrane Lipid ◽  
Lipid Biosynthesis ◽  
Transport Kinetics ◽  
Negative Effect ◽  
And Function

Recent biochemical and biophysical evidence have established that membrane lipids, namely phospholipids, sphingolipids and sterols, are critical for the function of eukaryotic plasma membrane transporters. Here, we study the effect of selected membrane lipid biosynthesis mutations and of the ergosterol-related antifungal itraconazole on the subcellular localization, stability and transport kinetics of two well-studied purine transporters, UapA and AzgA, in Aspergillus nidulans. We show that genetic reduction in biosynthesis of ergosterol, sphingolipids or phosphoinositides arrest A. nidulans growth after germling formation, but solely blocks in early steps of ergosterol (Erg11) or sphingolipid (BasA) synthesis have a negative effect on plasma membrane (PM) localization and stability of transporters before growth arrest. Surprisingly, the fraction of UapA or AzgA that reaches the PM in lipid biosynthesis mutants is shown to conserve normal apparent transport kinetics. We further show that turnover of UapA, which is the transporter mostly sensitive to membrane lipid content modification, occurs during its trafficking and by enhanced endocytosis, and is partly dependent on autophagy and Hect-type HulARsp5 ubiquitination. Our results point out that the role of specific membrane lipids on transporter biogenesis and function in vivo is complex, combinatorial and transporter-dependent.

scholarly journals Programmed ER fragmentation drives selective ER inheritance and degradation in budding yeast meiosis

2021 ◽  
Author(s):  
George M. Otto ◽  
Tia Cheunkarndee ◽  
Jessica M. Leslie ◽  
Gloria A. Brar
Keyword(s):  
Plasma Membrane ◽  
Cell Differentiation ◽  
Budding Yeast ◽  
Developmentally Regulated ◽  
Selective Degradation ◽  
Cell Plasma ◽  
Membrane Tethering ◽  
Membrane Bound ◽  
Yeast Meiosis ◽  
And Function

AbstractThe endoplasmic reticulum (ER) is a membrane-bound organelle with diverse, essential functions that rely on the maintenance of membrane shape and distribution within cells. ER structure and function are remodeled in response to changes in cellular demand, such as the presence of external stressors or the onset of cell differentiation, but mechanisms controlling ER remodeling during cell differentiation are not well understood. Here, we describe a series of developmentally regulated changes in ER morphology and composition during budding yeast meiosis, a conserved differentiation program that gives rise to gametes. During meiosis, the cortical ER undergoes fragmentation before collapsing away from the plasma membrane at anaphase II. This programmed collapse depends on the meiotic transcription factor Ndt80, conserved ER membrane structuring proteins Lnp1 and reticulons, and the actin cytoskeleton. A subset of ER is retained at the mother cell plasma membrane and excluded from gamete cells via the action of ER-plasma membrane tethering proteins. ER remodeling is coupled to ER degradation by selective autophagy, which is regulated by the developmentally timed expression of the autophagy receptor Atg40. Autophagy relies on ER collapse, as artificially targeting ER proteins to the cortically retained ER pool prevents their degradation. Thus, developmentally programmed changes in ER morphology determine the selective degradation or inheritance of ER subdomains by gametes.

scholarly journals Control of membrane fusion in exocytosis. Physiological studies on a Paramecium mutant blocked in the final step of the trichocyst extrusion process.

1980 ◽  
Vol 85 (2) ◽  
pp. 213-227 ◽  
Author(s):  
J Beisson ◽  
J Cohen ◽  
M Lefort-Tran ◽  
M Pouphile ◽  
M Rossignol
Keyword(s):  
Plasma Membrane ◽  
Membrane Fusion ◽  
Freeze Fracture ◽  
Acid Synthesis ◽  
Extrusion Process ◽  
Membrane Lipid ◽  
Effect Of Temperature ◽  
Physiological Studies ◽  
And Function ◽  
Induced Changes

Previous studies on exocytosis in Paramecium using mutants affecting trichocyst extrusion permitted us to analyze the assembly and function of three intramembrane particle arrays ("ring" and "rosette" in the plasma membrane, "annulus" in the trichocyst membrane) involved in the interaction between these two membranes. Using a conditional mutation, nd9, which blocks rosette assembly and prevents exocytosis at the nonpermissive temperature, we have analyzed the effect of temperature on the secretory capacity of nd9 cells. By combining several techniques (physiological studies, microinjections, inhibition of fatty acid synthesis, and freeze-fracture analysis) we demonstrate (a) that the product of the mutated allele nd9 is not thermolabile but that its activity is dependent upon temperature-induced changes in the membrane lipid composition and (b) that the product of the nd9 locus is a diffusible cytoplasmic component whose interaction with both plasma membrane and trichocyst membrane is required for rosette assembly and exocytosis. The data provide physiological evidence for the existence of a molecular complex(es) linking the two membranes and involved in the control of membrane fusion; we discuss the possible nature and function of these links.

scholarly journals Stat-mediated Signaling Induced by Type I and Type II Interferons (IFNs) Is Differentially Controlled through Lipid Microdomain Association and Clathrin-dependent Endocytosis of IFN Receptors

2006 ◽  
Vol 17 (7) ◽  
pp. 2896-2909 ◽  
Author(s):  
Marta Marchetti ◽  
Marie-Noelle Monier ◽  
Alexandre Fradagrada ◽  
Keith Mitchell ◽  
Florence Baychelier ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Biological Activities ◽  
Critical Role ◽  
Membrane Lipid ◽  
Endocytic Pathway ◽  
Type I ◽  
Type Ii ◽  
Biological Responses ◽  
Signal Specificity ◽  
Ifn Γ

Type I (α/β) and type II (γ) interferons (IFNs) bind to distinct receptors, although they activate the same signal transducer and activator of transcription, Stat1, raising the question of how signal specificity is maintained. Here, we have characterized the sorting of IFN receptors (IFN-Rs) at the plasma membrane and the role it plays in IFN-dependent signaling and biological activities. We show that both IFN-α and IFN-γ receptors are internalized by a classical clathrin- and dynamin-dependent endocytic pathway. Although inhibition of clathrin-dependent endocytosis blocked the uptake of IFN-α and IFN-γ receptors, this inhibition only affected IFN-α–induced Stat1 and Stat2 signaling. Furthermore, the antiviral and antiproliferative activities induced by IFN-α but not IFN-γ were also affected. Finally, we show that, unlike IFN-α receptors, activated IFN-γ receptors rapidly become enriched in plasma membrane lipid microdomains. We conclude that IFN-R compartmentalization at the plasma membrane, through clathrin-dependent endocytosis and lipid-based microdomains, plays a critical role in the signaling and biological responses induced by IFNs and contributes to establishing specificity within the Jak/Stat signaling pathway.

scholarly journals Fifteen years of research on oral–facial–digital syndromes: from 1 to 16 causal genes

2017 ◽  
Vol 54 (6) ◽  
pp. 371-380 ◽  
Author(s):  
Ange-Line Bruel ◽  
Brunella Franco ◽  
Yannis Duffourd ◽  
Julien Thevenon ◽  
Laurence Jego ◽  
...  
Keyword(s):  
Transition Zone ◽  
Genetic Disorders ◽  
Intraflagellar Transport ◽  
Heterozygous Mutation ◽  
Type I ◽  
Gene Encoding ◽  
Distinct Subgroup ◽  
Functional Studies ◽  
New Genes ◽  
Wide Range

Oral–facial–digital syndromes (OFDS) gather rare genetic disorders characterised by facial, oral and digital abnormalities associated with a wide range of additional features (polycystic kidney disease, cerebral malformations and several others) to delineate a growing list of OFDS subtypes. The most frequent, OFD type I, is caused by a heterozygous mutation in theOFD1gene encoding a centrosomal protein. The wide clinical heterogeneity of OFDS suggests the involvement of other ciliary genes. For 15 years, we have aimed to identify the molecular bases of OFDS. This effort has been greatly helped by the recent development of whole-exome sequencing (WES). Here, we present all our published and unpublished results for WES in 24 cases with OFDS. We identified causal variants in five new genes (C2CD3,TMEM107,INTU,KIAA0753andIFT57) and related the clinical spectrum of four genes in other ciliopathies (C5orf42,TMEM138,TMEM231andWDPCP) to OFDS. Mutations were also detected in two genes previously implicated in OFDS. Functional studies revealed the involvement of centriole elongation, transition zone and intraflagellar transport defects in OFDS, thus characterising three ciliary protein modules: the complex KIAA0753-FOPNL-OFD1, a regulator of centriole elongation; the Meckel-Gruber syndrome module, a major component of the transition zone; and the CPLANE complex necessary for IFT-A assembly. OFDS now appear to be a distinct subgroup of ciliopathies with wide heterogeneity, which makes the initial classification obsolete. A clinical classification restricted to the three frequent/well-delineated subtypes could be proposed, and for patients who do not fit one of these three main subtypes, a further classification could be based on the genotype.

Reciprocal functions of the Drosophila Yellow and Ebony proteins in the development and evolution of pigment patterns

Development ◽  
2002 ◽  
Vol 129 (8) ◽  
pp. 1849-1858 ◽  
Author(s):  
Patricia J. Wittkopp ◽  
John R. True ◽  
Sean B. Carroll
Keyword(s):  
Drosophila Melanogaster ◽  
Molecular Mechanisms ◽  
Rapid Evolution ◽  
Ectopic Expression ◽  
Melanin Formation ◽  
Body Coloration ◽  
And Function ◽  
Male Specific ◽  
Development And Evolution ◽  
Pigment Patterns

Body coloration affects how animals interact with the environment. In insects, the rapid evolution of black and brown melanin patterns suggests that these are adaptive traits. The developmental and molecular mechanisms that generate these pigment patterns are largely unknown. We demonstrate that the regulation and function of the yellow and ebony genes in Drosophila melanogaster play crucial roles in this process. The Yellow protein is required to produce black melanin, and is expressed in a pattern that correlates with the distribution of this pigment. Conversely, Ebony is required to suppress some melanin formation, and is expressed in cells that will produce both melanized and non-melanized cuticle. Ectopic expression of Ebony inhibits melanin formation, but increasing Yellow expression can overcome this effect. In addition, ectopic expression of Yellow is sufficient to induce melanin formation, but only in the absence of Ebony. These results suggest that the patterns and levels of Yellow and Ebony expression together determine the pattern and intensity of melanization. Based on their functions in Drosophila melanogaster, we propose that changes in the expression of Yellow and/or Ebony may have evolved with melanin patterns. Consistent with our hypothesis, we find that Yellow and Ebony are expressed in complementary spatial patterns that correlate with the formation of an evolutionary novel, male-specific pigment pattern in Drosophila biarmipes wings. These findings provide a developmental and genetic framework for understanding the evolution of melanin patterns.

scholarly journals Membrane Lipid Composition: Effect on Membrane and Organelle Structure, Function and Compartmentalization and Therapeutic Avenues

2019 ◽  
Vol 20 (9) ◽  
pp. 2167 ◽  
Author(s):  
Doralicia Casares ◽  
Pablo V. Escribá ◽  
Catalina Ana Rosselló
Keyword(s):  
Plasma Membrane ◽  
Lipid Bilayers ◽  
Lipid Composition ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Signal Propagation ◽  
Membrane Lipid ◽  
Membrane Lipid Composition ◽  
Cell Functions ◽  
And Function

Biological membranes are key elements for the maintenance of cell architecture and physiology. Beyond a pure barrier separating the inner space of the cell from the outer, the plasma membrane is a scaffold and player in cell-to-cell communication and the initiation of intracellular signals among other functions. Critical to this function is the plasma membrane compartmentalization in lipid microdomains that control the localization and productive interactions of proteins involved in cell signal propagation. In addition, cells are divided into compartments limited by other membranes whose integrity and homeostasis are finely controlled, and which determine the identity and function of the different organelles. Here, we review current knowledge on membrane lipid composition in the plasma membrane and endomembrane compartments, emphasizing its role in sustaining organelle structure and function. The correct composition and structure of cell membranes define key pathophysiological aspects of cells. Therefore, we explore the therapeutic potential of manipulating membrane lipid composition with approaches like membrane lipid therapy, aiming to normalize cell functions through the modification of membrane lipid bilayers.

Overexpressed Gliotactin activates BMP signaling through interfering with the Tkv–Dad association

Genome ◽  
2020 ◽  
pp. 1-12
Author(s):  
Zohreh Sharifkhodaei ◽  
Vanessa J. Auld
Keyword(s):  
Mrna Level ◽  
Ectopic Expression ◽  
Inhibitory Effect ◽  
Bmp Signaling ◽  
Type I ◽  
Protein Levels ◽  
Barrier Formation ◽  
Epithelial Junctions ◽  
Pupal Wing ◽  
And Function

Epithelial junctions ensure cell–cell adhesion and establish permeability barriers between cells. At the corners of epithelia, the tricellular junction (TCJ) is formed by three adjacent epithelial cells and generates a functional barrier. In Drosophila, a key TCJ protein is Gliotactin (Gli) where loss of Gli disrupts barrier formation and function. Conversely, overexpressed Gli spreads away from the TCJ and triggers apoptosis, delamination, and cell migration. Thus, Gli protein levels are tightly regulated and by two mechanisms, at the protein levels by tyrosine phosphorylation and endocytosis and at the mRNA level through microRNA-184. Regulation of Gli mRNA is mediated through a Gli–BMP–miR184 feedback loop. Excessive Gli triggers BMP signaling pathway through the activation of Tkv type-I BMP receptor and Mad. Elevated level of pMad induces micrRNA-184 expression which in turn targets the Gli 3′UTR and mRNA degradation. Gli activation of Tkv is not through its ligand Dpp but rather through the inhibition of Dad, an inhibitory-Smad. Here, we show that ectopic expression of Gli interferes with Tkv–Dad association by sequestering Dad away from Tkv. The reduced inhibitory effect of Dad on Tkv results in the increased Tkv–pMad signaling activity, and this effect is continuous through larval and pupal wing formation.

Type I Interferons promote maintenance and function of follicular T helper cells in vitro

2019 ◽  
Author(s):  
S Ehrlich ◽  
K Wild ◽  
M Smits ◽  
K Zoldan ◽  
M Hofmann ◽  
...  
Keyword(s):  
T Helper Cells ◽  
Type I Interferons ◽  
Type I ◽  
T Helper ◽  
Helper Cells ◽  
Follicular T Helper Cells ◽  
And Function
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