Cellular communications and signaling

The EU will first address the main communication pathways between normal cells and intracellular transduction pathways encountered in physiological and neurophysiological mechanisms. Thus, G protein-coupled receptors (GPCRs) will be studied, namely their structure, function, and modulation by interaction proteins involved in particular in the phenomenon of desensitization. The main intracellular pathways activated by membrane GCRs will be addressed (MAP kinase pathways, PI3 kinase, etc.).

Next, a significant portion of the course will focus on calcium signaling and Ca2+ homeostasis, Ca2+ being a ubiquitous signal in cellular signaling. Calcium homeostasis will be studied in particular during the response of lymphocytes after antigen stimulation. Furthermore, the production of oxygen free radicals, which cause oxidative stress, is dependent on intracellular Ca2+. The physiological role of free radicals will be discussed, as well as their involvement in oxidative stress. In this context, the pathways of protection against oxidative stress will also be studied.The following chapter will address the endocannabinoid system, which will allow us to recap all the topics previously discussed in the course. The endocannabinoid system is responsible for multiple central and peripheral regulations.

Finally, two other topics will be addressed: the blood-brain barrier, which allows for highly integrated cellular communication between two environments, and the pancreatic β-cell, whose activity is crucial for regulating blood sugar levels through insulin secretion.

The EU's objective is to

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

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

-develop scientific arguments with a critical approach to experimental results (analysis of data from publications related to the topics covered in the course). The concept of experimental models will be discussed.

Obtaining a license providing basic knowledge of cellular communication: concept of membrane receptors and intracellular transduction pathways.

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 elements of cellular communication: receptors, ion channels, extracellular matrix.

-Multiple transduction pathways

-Pharmacology reminders

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

-Main families of RCPG-Proteins interacting with RCPGs (GIP)

-Desensitization mechanism: action of GRKs and arrestins

-Phenomena of tolerance and dependence on opiates

-Concept of a 'biased' agonist

-Oligomerization of RCPGs

-Genetic diseases associated with RCPG mutations

3-The calcium signal

-Methodological approaches: fluorescent probes.

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

-The path of nitrogen monoxide

4-Ways to resist oxidative stress

-generation of oxygen radicals

-activation of the Nrf2 pathway

5-The endocannabinoid and endovanilloid systems

-discoveries of eCB receptors and ligands

-biosynthesis and degradation of eCBs

-roles in the regulation of neurotransmission and behavioral activity

-role in food intake

6-The blood-brain barrier

-cellular and molecular aspects

-studies of the permeability of the BHE

7-Examples of signal integration: the pancreatic β-cell

-regulation of insulin release

-mechanism of action of the main antidiabetic drugs