- Know the general mechanisms of cell signaling (procedures, types of signals, effectors, receptors, second messengers)
- Deepen certain channels and their relationships with certain diseases and metabolic regulation
- Become familiar with the areas of protein-protein interaction and anchoring proteins involved in signaling.
- Have a notion of the techniques used to study cell signaling components (marking techniques, use of probes, pharmacological tools, etc ...).
Part I: GENERAL PRINCIPLES OF INTERCELLULAR COMMUNICATION.
1-1 Signaling and cell function
1-2 Terms of cellular communication (type junctions "gap", adhesion molecules, chemical signals).
1-3 Cellular communication by a chemical signal: autocrine, paracrine communication, endocrine and synaptic communication.
1-4 Chemical signals: Free radicals gaseous hydrophobic molecules, water-soluble molecules
1-5 Surface protein receptors: receptors ligand-gated ion channels, receptors "enzymes" G- protein-coupled receptors.
1-6 Signal transduction soluble chemical.
1-7 The network of intracellular signaling molecules.
Part II: DYNAMIC INTERACTIONS IN PROTEIN-PROTEIN SIGNALING
II. 1. Protein domains: Overview of protein domains with specific examples of their implications in cellular signaling: tyrosine phosphorylated binding proteins (SH2, PTB, 14-3-3), binding domains proline-rich regions (SH3) recognition domains of phosphoinositide membrane (PH) proteins activated or inactivated by phosphorylation (PKA, PKC, phosphatase), GTP-binding proteins, binding proteins Ca + + (EF), C2 (homologous binding domain of the Ca + + in PKC).
Part III: SIGNALLING MEDIATED BY METABOLITES
III.1. Signaling associated with Glucose: Regulation of the release and synthesis of insulin by glucose, transcriptional regulation in response to glucose. Signaling cascade via the insulin receptor; Inositol phosphate and the role of membrane lipids.
III.2. Signaling associated with fatty acids: PPARs, prostaglandins (PGs), thromboxanes (TXs).
III.3. Cellular aspects: regulation of GLUT 4 membrane cycle; mTOR.
III.4. Signaling associated with steroid hormone, thyroid hormone, retinoid and orphan type receptors.
Part IV: MOLECULAR SIGNALING PATHWAYS.
IV-A-VESICULAR TRAFFIC, SECRETION, AND ENDOCYTOSIS.
1. Techniques for studying the secretory pathway.
2. Molecular mechanisms of vesicular traffic.
3. Early stages of the secretory pathway.
4. Later stages of the secretory pathway.
5. Receptor-mediated endocytosis.
6. Directing membrane proteins and cytosilic materials to the lysosome.
IV-B-CELL SIGNALING I:SIGNAL TRANSDUCTION AND SHORT-TERM CELLULAR RESPONSES.
1. From extracelluar signal to cellular response.
2. Studying cell-surface receptors.
3. Highly conserved components of intracellular signal-transduction pathways.
4. General elements of G-protein-coupled receptor systems.
5. Protein-coupled receptors that regulate lon channels.
6. Protein-coupled receptors that activate or inhibit adenylyl cyclase.
7. Protein-coupled receptors that activate phospholipase c.
8. Integrating responses of cells to environmental influences.
IV-C-CELL-SIGNALING II: SIGNALING PATHWAYS THAT CONTROL GENE ACTIVITY
1. TGFB receptors and the direct activation of smads.
2. Cytokine receptors and the JAK/STAT pathway.
3. Receptor tyrosine kinases (RTK).
4. Activation of RAS and MAP kinase pathways.
5. Phosphoinositides as signal transducers.
6. Activation of gene transcription by seven- spanning cell-surface receptors.
7. Pathways that involve signal-induced protein cleavage (NF-KB).
IV-D- CELL-SIGNALING III: CELL ORGANIZATION AND MOVEMEMT
1. Microfilaments and actin structures.
2. Dynamiics of actin filments.
3. Mechanisms of actin filament assembly.
4. Organization of actin-based cellular structures.
5. Myosins: actin-bassed motor proteins.
6. Myosin-powered movements.
7. Cell migration:signaling and chemotaxis.
IV-E- CELL-SIGNALING IV: CELL ORGANIZATION AND MOVEMENT.
1. Microtubule structure and organization.
2. Microtubule dynamics.
3. Regulation of microtubule structure and dynamics.
4. Kinesins and dyneins:microtubule-based motor proteins.
5. Cilia and flagella:microtubule-bassed surface structures.
7. Intermediate filaments.
8. Coordination and cooperation between cytoskeletal elements.
IV-F- CELL-SIGNALING V: INTEGRATING CELLS INTO TISSUES.
1. Cell-celland cell-matrix adhesion:an overview.
2. Cell-cell and cell-ECM junctions and their adhesion molecules.
3. The extracellular matrix I: the basal lamina.
4. The extracellular matrix II: connective and other tissues.
5. Adhesive interactions in motile and nonmotile cells .
IV-G- CELL-SIGNALING VI: REGULATING THE CELL EUKARYOTIC CELL CYCLE.
1. Overview of the cell cycle and its control.
2. Control of mitosis by cyclins and MPF activity.
3. Cyclin-dependent kinase regulation during mitosis.
4. Molecular mechanisms for regulating mitotic events.
5. Cyclin-CDK and ubiquitin-protein ligase control of s phase.
6. Cell-cycle control in mammalian cells.
7. Checkpoints in cell-cycle regulation.
Part V: SIGNALLING RELATED TO STRESS, SURVIVAL AND CELL DEATH.
V.1. Ubiquitin-proteasome pathways in signaling: Ubiquitin and SUMO systems in the regulation of cell cycle regulation of HIF: prolyl hydroxylases, the ubiquitin - proteasome and cancer.
IV.2. Extrinsic and intrinsic pathways of apoptosis: receptors involved in cell death family protein Bcl-2 mitochondria, mitochondrial membrane permeability; Shares pro-and anti-apoptotic of GSK3, protein and caspases CARD; Interaction between channels e apoptotic pathways induced by stress (heat shock proteins).
IV.3. Signaling pathways involved in cell survival: JAK-STAT mitochondrial hexokinases; mTOR; survival signaling in cancer.
At the end of this course, the student should be able to:
- To understand and assimilate the major signaling pathways at the molecular level and their implications in various pathologies.
- To approach the study of these pathways by familiarizing themselves with the means and techniques to this topic.
- Understand the choice of therapy in certain diseases (mechanisms of action of some drugs.
The tutorials consist primarily of the analysis of documents and publications coming illustrate, supplement and deepen some important points of the course. They should enable students to better know how to organize, manage and present a literature search (effort sorting information obtained through different channels and synthesis, use of computer tools for the presentation).
1. Cell signalling (second edition), John T. HANCOCK. . Oxford University Press.
2. Molecular cell biology 6th and 7th edition. Editor Lodish et al ( 2008 and 2012) WH freeman and Co.
3. Signal transduction. Bastien D. GOMPERTS, Ijsbrand M. KRAMER et Peter E.R. TATHAM. Elsevier Academic Press