Phosphatidylinositol

Un phosphatidylinositol est un phospholipide, constituant des membranes cellulaires. Il se trouve préférentiellement sur la face interne de la bicouche lipidique. Cette molécule est composée d'un acide phosphatidique (deux acides gras estérifiant une molécule de glycérol, elle-même liée de façon covalente à un acide phosphorique) dont le groupement phosphate est associée à une molécule de , un polyol cyclique : upright=1.25|gauche|vignette|Structure générique d'un phosphatidylinositol. Il est activé par deux molécules d'ATP (donnant deux molécules d'ADP) en phosphatidylinositol-4,5-bisphosphate. Par l'intermédiaire de la , il est clivé en diacylglycérol (DAG, qui active la protéine kinase C) et en inositol-1,4,5-trisphosphate (IP3 ; le premier phosphate provient du phospholipide) qui ouvre les canaux Ca2+ intracellulaires. Cette réaction libère de l'eau. La réponse de cette hydrolyse est l'activation d'enzymes, de messages hormonaux… Il est fortement polaire avec une charge nette

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The role of the phosphoinositides at the Golgi complex

Eukaryotic cells are organized into a complex system of subcompartments, each with its distinct protein and lipid composition. A continuous flux of membranes crosses these compartments, and in some cases direct connections exist between the different organelles. It is thus surprising that they can maintain their individual identities. Small GTPases and the phosphoinositides have emerged as the key regulators in the maintenance of the identity of the Golgi complex. This property is due to their ability to act either alone or, more often, in combination, as cues directing and controlling the recruitment of proteins that possess phosphoinositide-binding domains. Among these many proteins there are the lipid transfer proteins, which can transfer ceramide, oxysterol, cholesterol and possibly glucosylceramide. By regulating these lipid transfer proteins in this way, this binomial combination of the small GTPases and the phosphoinositides acquires a further important role: control of the synthesis and/or distribution of other important integral constituents of cell organelles, such as the sphingolipids and cholesterol. This role is particularly relevant at the level of the Golgi complex, a key organelle in the biosynthesis, transport and sorting of both lipids and proteins that is located at the intersection of the secretory and endocytic pathways.

2007

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Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase

Charlotte Julie Caroline Gehin, Sandrine Madeleine Suzanne Georgeon, Barbara Gerig, Oliver Hantschel, Tim Kükenshöner, Sara Raquel Pereira Pinho, Florence Pojer, Sina Maren Reckel, Delphine Maude Tardivon

The two isoforms of the Bcr-Abl tyrosine kinase, p210 and p190, are associated with different leukemias and have a dramatically different signaling network, despite similar kinase activity. To provide a molecular rationale for these observations, we study the Dbl-homology (DH) and Pleckstrin-homology (PH) domains of Bcr-Abl p210, which constitute the only structural differences to p190. Here we report high-resolution structures of the DH and PH domains and characterize conformations of the DH-PH unit in solution. Our structural and functional analyses show no evidence that the DH domain acts as a guanine nucleotide exchange factor, whereas the PH domain binds to various phosphatidylinositol-phosphates. PH-domain mutants alter subcellular localization and result in decreased interactions with p210-selective interaction partners. Hence, the PH domain, but not the DH domain, plays an important role in the formation of the differential p210 and p190 Bcr-Abl signaling networks.

Springer Nature2017

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The multiple roles of PtdIns(4)P - not just the precursor of PtdIns(4,5)P2

The phosphoinositides (PIs) are membrane phospholipids that actively operate at membrane-cytosol interfaces through the recruitment of a number of effector proteins. In this context, each of the seven different PI species represents a topological determinant that can establish the nature and the function of the membrane where it is located. Phosphatidylinositol 4-phosphate (PtdIns(4)P) is the most abundant of the monophosphorylated inositol phospholipids in mammalian cells, and it is produced by D-4 phosphorylation of the inositol ring of PtdIns. PtdIns(4)P can be further phosphorylated to PtdIns(4,5)P(2) by PtdIns(4)P 5-kinases and, indeed, PtdIns(4)P has for many years been considered to be just the precursor of PtdIns(4,5)P(2). Over the last decade, however, a large body of evidence has accumulated that shows that PtdIns(4)P is, in its own right, a direct regulator of important cell functions. The subcellular localisation of the PtdIns(4)P effectors initially led to the assumption that the bulk of this lipid is present in the membranes of the Golgi complex. However, the existence and physiological relevance of ;non-Golgi pools' of PtdIns(4)P have now begun to be addressed. The aim of this Commentary is to describe our present knowledge of PtdIns(4)P metabolism and the molecular machineries that are directly regulated by PtdIns(4)P within and outside of the Golgi complex.

2008

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Phospholipide

vignette|Représentation schématique de quelques phosphoglycérides. A. phosphatidylcholine, B. phosphatidyléthanolamine, C. phosphatidylsérine,&nb

Membrane plasmique

La membrane plasmique, également appelée membrane cellulaire, membrane cytoplasmique, voire plasmalemme, est une membrane biologique séparant l'intérieur d'une cellule, appelé cytoplasme, de son envir

Inositol trisphosphate

L’inositol trisphosphate, souvent appelé trisphosphoinositol et abrégé , est, avec les diacylglycérols (DAG), un messager secondaire de la transduction de signal et de la signalisation lipidique des

BIO-207: Cellular and molecular biology II

This course is aimed to familiarize students with the 3D organization of a eukaryotic cell, its compartmentalization, how cellular compartments communicate together and how a cell communicates with its environment. The related molecular mechanisms will be discussed.

CH-210: Biochemistry

Les constituants biochimiques de l'organisme, protéines, glucides, lipides, à la lumière de l'évolution des concepts et des progrès en biologie moléculaire et génétique, sont étudiés.

BIO-310: Immunology

Ce cours décrit le fonctionnement du système immunitaire humain et les bases immunologiques de la vaccination, de la transplantation, de l'immunothérapie, et de l'allergie. Il présente aussi le rôle des cellules souches dans la formation des tissus, notamment la lignée hématopoïétique.