Cellular communications and signalling

The main communication pathways between normal cells and the intracellular transduction pathways encountered in physiological and neurophysiological mechanisms will be covered, with a focus on G protein-coupled receptors (GPCRs) and their structure, function and modulation by interacting proteins, notably involved in desensitization. The main intracellular pathways activated by GPCRs will be discussed (MAPkinase, PI3kinase, etc.).

A major part of the course will then focus on calcium signaling and Ca2+ homeostasis, Ca2+ being a ubiquitous signal in cell signaling. Calcium homeostasis will be studied in particular during the lymphocyte response to antigenic stimulation. In addition, the production of oxygenated free radicals, at the origin of oxidative stress, is dependent on intracellular Ca2+. The physiological role of free radicals will be discussed, as well as their involvement in oxidative stress. The following chapter will focus on the endocannabinoid system, summarizing all the topics covered earlier in the course. The endocannabinoid system is at the origin of multiple central and peripheral regulations.

Finally, two other themes will be addressed: the blood-brain barrier, which evokes highly integrated cellular communication between two environments, and the -pancreatic cell, whose activity is crucial to the regulation of glycemia through insulin secretion.

The EU's objective is to

-enable students to acquire current knowledge of the molecular mechanisms of intercellular and intracellular communication, using specific examples of cellular models.

-describe the methodological approaches used to decipher the signals used for cellular communication.

-develop a scientific argument with a critical approach to experimental results (analysis of data from publications relating to the topics covered in the course).

Bachelor's degree giving basic knowledge of cellular communication: notion of membrane receptor and intracellular transduction pathway.

Recommended prerequisites: Basic knowledge of the molecular mechanisms involved in major physiological and neurophysiological functions. Basic knowledge of pharmacology.

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1-Introduction:

-Membrane components of cell communication: receptors, ion channels, extracellular matrix.

-Multiple transduction pathways

-Pharmacology reminder

2-Signals activated by G protein-coupled receptors (GPCRs):

Main families of GPCRs-GPCR-interacting proteins (GIPs)

-Desensitization mechanism: GRK and arrestin action

-Tolerance phenomena and opiate dependence

-Notion of 'biased' agonist

-Oligomerization of RCPGs

-Genetic diseases associated with GPCR mutations

3-The calcium signal

-Methodological approaches: fluorescent probes.

-Application: calcium homeostasis in immune cells (capacitive calcium entry mechanism) and lymphocyte response.

-The nitric oxide pathway

4-Oxidative stress resistance pathways

-generation of oxygen radicals

-activation of the Nrf2 pathway

5-The endocannabinoid and endovanilloid systems

-discovery of eCB receptors and ligands

-eCB biosynthesis and degradation

-roles in regulating neurotransmission and behavioral activity

-role in food intake

6-The blood-brain barrier

-cellular and molecular aspects

-studies of BBB permeability

7-Examples of signal integration: cellule-pancreatic

-regulation of insulin release

-Mechanism of action of the main anti-diabetic agents