Cellular Communications and Signaling

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

Next, a significant portion of the course will focus on calcium signaling and Ca²⁺ homeostasis, as Ca²⁺ is a ubiquitous signal in cellular signaling. Calcium homeostasis will be studied in particular in the context of the lymphocyte response following antigenic 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 protective mechanisms against oxidative stress will also be examined.The following chapter will address the endocannabinoid system, which serves to summarize all the topics previously covered in the course. The endocannabinoid system is responsible for numerous central and peripheral regulatory processes.

Finally, two other topics will be covered: the blood-brain barrier, which provides a framework for discussing cellular communication in a highly integrated manner between two environments, and the pancreatic β-cell, whose activity is crucial for regulating blood glucose levels through insulin secretion.

The EU's goal is to

-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 involved in cellular communication.

-Develop a scientific argument based on a critical analysis of experimental results (analysis of data from publications related to the topics covered in the course). The concept of an experimental model will be discussed.

Earned a bachelor's degree providing foundational knowledge in cellular communication: the concepts of membrane receptors and intracellular signaling 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 components of cellular communication: receptors, ion channels, extracellular matrix.

-Multiple signaling pathways

-Pharmacology Review

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

-Major families of RCPGs—Proteins that interact with RCPGs (GIP)

-Desensitization mechanism: action of GRKs and arrestins

-Tolerance and Dependence on Opioids

-“Biased” agonist concept

-Oligomerization of RCPGs

-Genetic disorders 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 Nitric Oxide Pathway

4 Ways to Combat Oxidative Stress

-formation of oxygen radicals

-activation of the Nrf2 pathway

5-The Endocannabinoid and Endovanilloid Systems

-Discoveries regarding eCB receptors and ligands

-biosynthesis and degradation of eCBs

-roles in the regulation of neurotransmission and behavioral activity

-role in feeding

6. The blood-brain barrier

-cellular and molecular aspects

-Studies of the permeability of the blood-brain barrier

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

-regulation of insulin release

-Mechanism of action of the main antidiabetic drugs