intercellular communication through chemical signals


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 :

    1. 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.
    2. 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.
    3. 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.
Figure 01. the 4 intercellular communication modes by chemical signals.

(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… )

Figure 02. Signal transduction by water-soluble molecules.

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.

  1. G protein-coupled receptors.
  2. enzymes receptors.
  3. 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.

Figure 03. General schematic structure of G-protein coupled receptors.

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.

Figure 04. GPCRs are able to recognize extremely diverse ligands (photons, ions, odorants, peptides, lipids, protein…).

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.
Figure 05. Ligand binding to its specific receptor (RCPG) active G protein (Gs) which establishes a GTP molecule by the unit under a, which leads to dissociation of the complex "Py. The unit was activated in I7adenylate stimulates cyclase, enzyme capable of converting ATP into cAMP. The molecules of cAMP produced in significant quantities act as second messengers responsible amplification of the signal and transmitting the message inside the cell. (Example : Adrenaline, glucagon, ACTH…).
  • Example 2 : signaling pathway by phospholipase C
Figure 06. Ligand binding to its specific receptor (muscanmque) causes the activation of phospholipase C via G protein (Gq, subunit), which leads to the formation of two second messengers, l’inositol 1,4,5 triphosphate (IP3) and diacylglycerol (DAY). The IP3 migre the inténeur the cells and s'attache sur ces récepteurs spécifiques (Ca ++ ligand dependent channels) located on the RE membrane resulting in the release of Ca ++ in the cytosol. As for the DAG, it remains bound to the plasma membrane and the active lanase C protein which is responsible for a phosphorylation cascade. Example ligands (Acetylcholine receptor on its muscanmque. Histamine ).

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).

Figure 07. Structure of membrane receptor tyrosine kinase activity.

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).

Figure 08. Ligand binding (L) receptor (R) leads to dimerization in the case of monomeric receptors (one growth factor such). Some receivers are starting dimeric ; of the 1 Insulin has two sub- units extracellular, related to two transmembrane subunits p by disulfide bridges. L & rsquo; cross autophosphorylation of the intracellular catalytic domains allows & rsquo; activation by phosphorylation of substrate proteins (PS) having different biological activities, and which typically triggers a cascade of phosphorylation.
Figure 09. membrane receptor activity guanylate cyclase. Binding of ligand to the receptor activates the guanylate cyclase activity of the intracellular domain which leads to the synthesis of GMPcyclique which acts as a second messenger. Example ligands : Peptide atrial natriurétique (ANP).

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).

Figure 10. To the left, structure of the acetylcholine receptor (5 subunits). To the right, operation of receiver channel (A), and structure of each subunit (B). Noting also that two acetylcholine molecules attach to the sub units.

Course of DR AOUATI Amel – Faculty of Constantine