1- Introduction :
Intercellular communication is one of the features of multicellular organisms, provided by chemical molecules (informative or messengers molecules) issued by a cell (said transmitter) and recognized by another cell (said receiver). This communication directs the fundamental cell process, coordinates their activity and allows the different cells of the body to perceive their microenvironment.
2- The different communication strategies by chemical signals :
On distingue 4 types of intercellular communication: La communication endocrine, paracrine, autocrine and chemical synaptic (figure 01).
3- Overview of informational molecules and their receptors :
An information molecule is a synthesized chemical molecule and secreted by a said cell secretory and acts on another receiving said cell (target) by interacting with specific molecules. Intercellular communication involves 3 main types of chemical signals :
- The water-soluble molecules informative : They act through specific receptors located at the plasma membrane of the target cell. This is the case of neurotransmitters, des cytokines, peptide hormones.
- The fat-soluble molecules informative : These molecules cross the lipid bilayer of the target cell by simple diffusion and act on intracellular receptors. This is the case of steroid hormones (cortisol and sex hormones) and thyroid hormone.
- The gaseous free radicals : The best known is the nitric oxide (NO). Their characteristic is to freely diffuse through the plasma membrane and act directly on the cytosolic enzymes, without the intervention of membrane or intracellular receptors.
(1). When endocrine communication, hormones produced by endocrine glands are secreted into the blood stream, and can be widely distributed throughout the body (example: insulin, glucagon…). (2). When paracrine communication, the chemical signal is released into the extracellular medium and acts only on the neighboring cells : it is a local chemical mediator (example : growth factors of & rsquo; vascular endothelium (VEGF), cytokines). (3). When autocrine communication, the cell secretes a signal which acts on one of its own receptors. The chemical mediator is local (example : Cytokines, epidermal growth factors (EGF)). (4). During chemical communication svnapticiue, the first messenger (neurotransmitter) is released by the presynaptic element and acts only on the post-synaptic a specialized nearby junction element (synapses intemeuronales, neuromuscular), without signal dispersion, what distinguishes communication by endocrine pathway (example : choline acetyl, noradrenaline… )
The informational molecule attaches to a specific membrane receptor which triggers signal transduction. The signal is transmitted to the & rsquo; inside the cell by a conformational change of the intracellular portion of the receptor or triggering its enzymatic activity (sometimes the receptor is an ion channel ligand-dependent). This change in conformation or function then induces & rsquo; initialization of various signaling pathways typically by & rsquo; via secondary messengers (second messengers).
4- Membrane receptors of soluble molecules and their diversity :
A membrane receptor can be defined as a molecular structure (protein, often a glycoprotein) that interacts specifically with a "messenger" (hormone, growth factor, neurotransmitters ..). This interaction creates a change in the receptor leading to a cellular response (transduction du signal). It includes an extracellular part (hydrophilic block) where is the recognition site and fixing
informative molecule, a transmembrane portion (hydrophobic sequence) and an intracellular effector function involved in party (transduction du signal).
On distingue 3 major types of membrane receptors.
- G protein-coupled receptors.
- enzymes receptors.
- ion channel receptors.
A- G protein-coupled receptors (RCPG) :
GPCRs are transmembrane proteins (glycoproteins) indirectly controls the activity of a target protein bound to the plasma membrane (an enzyme or an ion channel) via a heterotrimeric G protein.
The GPCR is a polypeptide chain with seven transmembrane hydrophobic segments (TM1 to TM7), connected by three intracellular loops (II, 12, 13) and three extracellular loops (The, E2, E3). A disulfide bridge connects El to E2. L & rsquo; amino terminus (NH2) is extracellular, l & rsquo; carboxy-terminus (COOH) is intracellular. The latter can introduce a lipid anchor into the membrane, which creates a fourth loop, 14. Noting also that the extracellular domain is always glycosylated.
After ligand binding domain on the extra cellular GPCR, the intracellular domain changes its conformation and activates a heterotrimeric G protein (a,p,Y) which hydrolyzes GTP (Guanosine triphosphate) followed by separation of subunits a and py. G protein transmits the signal to membrane enzymes (adenylyl cyclase, phospholipase C, phosphocüestérase…), or ion channels that act as primary effector. The primary effector activation leads to the production of second messengers (AMPc, Inositol triphosphat. Diacylglycerol, Ca ++ …) responsible for transmission of the signal within the cell.
Noting also that the activation of the primary G protein effector is done either by the subunit or subunits of the complex p,Y.
Protein G is a heterotrimeric protein anchored in the inner leaflet of the plasma membrane. It exists in 3 large classes : Gs : stimulated adenylate cyclase. Give : Inhibits adenylate cyclase. Gq : stimulates phospholipase C.
- Example 1 : adenylate cyclase-cyclic AMP pathway.
- Example 2 : signaling pathway by phospholipase C
B- Enzymes receptors (Enzymatically active) :
Enzyme receptors have a single transmembrane domain, glycosylated extracellular domain and an intracellular domain with enzymatic activity (or associated with an enzyme).
These receptors exist in 4 large classes:
a) the receptor kinase activity (Tyrosine, serine / threonine”)
b) the phosphatase activity to receptors (Tyrosine. serine / threonine).
c) Coupled receptors kinaseslTvrosine. histidine”)
d) the guanylates cyclases transmembranaires (synthetic GM Pc).
In the inactive state, these receptors are found as monomers in the plasma membrane, with the exception of some receptors such as the insulin receptor and 1TGF1. Ligand binding induces receptor dimerization (dimer formation). (EGF: The epidermal growth factor. PDGF: Growth factor platelet derived: N GF: The nerve growth factor: Insulin-like GF1 : growth factor 1 like the & rsquo; insulin).
C- ion channel receptors :
Have ionic ligand -dependent channels, which constitute a superfamily of receptor multimeric, which each monomer has 4 transmembrane domains.
Example : nicotinic acetylcholine receptor P (figure 10).
Course of DR AOUATI Amel – Faculty of Constantine