Cell communication S-114.2500 Cellbiosystems Olli-Pekka Koistinen 28.11.2007
Cell communication Cellbiosystems? What does it mean? Large groups of cells interacting with each other? Complex cell communication mechanisms have been essential for the evolution of multicellular organisms
1. Extracellular signal molecules cell communication systems are based on hundreds of kinds of extracellular signal molecules produced by cells to signal to other cells small peptides, amino acids, nucleotides, retinoids, steroids, fatty acid derivatives, gas molecules etc... most of them are released by exocytosis or diffusion through the plasma membrane, and some remain bound to the surface of the signalling cell
2. Receptor a specific protein that binds the signal molecule most of them are transmembrane proteins some are inside the target cell (the signalling molecule must be small or hydrophobic) when they are activated by the signal molecule, they start intracellular signalling pathways
3. Intracellular signalling proteins distribute the signal to different parts of the cell form different signalling pathways at the end of the pathway there is a target protein, which changes the cell behaviour
Forms of cell-to-cell signalling 1. Contact-dependent signalling signal molecules bound to the signalling cell surface 2. Paracrine signalling (short range) signal molecules act as local mediators and are often taken up by neighbouring cells, immobilized by the extracellular matrix or destroyed by extracellular enzymes 3. Synaptic signalling (fast and precise) nerve cells 4. Endocrine signalling (slower and less precise) signal molecules are hormones secreted by endocrine cells that drift in the bloodstream
... Autocrine signalling the cell sends signals that can bind to its own receptors utilized in development to reinforce some developmental process cancer cells use it to survive and proliferate in foreign environments Cell-cell gap junctions connect the cytoplasmas of neighbouring cells by narrow water channels the importance in communication is uncertain
The basis of specific responding typical cell recognizes hundreds of different signalling molecules, which can act as millions of combinations these combinations are responded selectively, according to the specific character of the target cell, which has developed in the cell specialization in addition, the cell may respond to combinations by differentiating or multiplying or by using some specialized function like contraction or secretion so in principle, there are almost unlimited amount of different signal combinations, and this enables animals to control their cells in extremely specific ways
The basis of specific responding the same signal molecule can affect on different target cells even in opposite ways even if the receptor proteins were identical, the effect can still be different because of different intracellular machinery acetylcholine decreases the force of contraction in the case of heart muscle cells but increases it in the case of skeletal muscle cells
Membrane-passing signalling molecules most extracellular signal molecules bind to receptors on the surface of the target cell, but some are hydrophobic or small enough to get through the plasma membrane: gases like nitric oxide and carbon dioxide (small) work by stimulating intracellular enzymes (guanylyl cyclase) steroid hormones, thyroid hormones, retinoids and vitamin D (hydrophobic) bind to intracellular proteins (nuclear receptors) that directly regulate specific gene transcription by binding to DNA can persist much longer than water-soluble signalling molecules in extracellular fluids, where they move with the help of certain carrier proteins
Cell-surface receptors water-soluble signal molecules work by binding to cell-surface receptor proteins these receptors are so called signal transducers, as in they convert the extracellular ligand binding into intracellular signals the largest classes of cell-surface receptor proteins: ion-channel-linked receptors G-protein-linked receptors enzyme-linked receptors
Ion-channel-linked receptors also known as transmitter-gated ion channels and ionotropic receptors large family of homologous, multipass transmembrane proteins acting as ion channels are opened and closed by a small amount of neurotransmitters binding to them activation changes the ion permeability of the plasma membrane and the excitability of the postsynaptic cell
G-protein-linked receptors use a separate cell-surface protein, like an enzyme or an ion channel, to regulate the cell behaviour a third protein, called a trimeric GTP-binding protein (G protein) mediates the interaction between these two plasma-membranebound proteins all the G-protein-linked receptors belong to a large family of homologous, seven-pass transmembrane proteins
Enzyme-linked receptors either act as enzymes or are associated with enzymes activating them single pass transmembrane proteins, the ligand-binding site outside and the catalytic or enzyme-binding site inside the cell majority of them are protein kinases or at least associated with them, which means that when ligand binds to them, a specific combination of proteins phosphorylates this class still not as homologous in structure as the two first classes of cell-surface receptor proteins
Intracellular signalling proteins both G-protein-linked and enzyme-linked receptors send the received signals into the cell interior by a chain of intracellular signalling events these chains contain both small intracellular mediators or second messengers and large intracellular signalling proteins the small second messengers are produced in large amounts and they are fast to diffuse and carry the signal to other parts of the cell the large signalling proteins can work by producing small intracellular mediators or relaying the signal to another signalling protein can be roughly divided to following seven groups according to their functions:
Intracellular signalling proteins 1. Relay proteins move the signal to the next member in the chain 2. Messenger proteins transport the signal between different parts of the cell 3. Amplifier proteins increase the signal by activating large amounts of signal molecules 4. Transducer proteins change the form of the signal 5. Bifurcation proteins spread the signal to other pathways 6. Integrator proteins unite signals from two or more pathways 7. Latent gene regulatory proteins are activated at the cell surface and move to the nucleus to trigger gene transcription
Intracellular signalling proteins In addition, there are some other intracellular proteins that affect on the signalling pathway: modulator proteins modify signalling protein activity adaptor proteins bind signalling proteins together anchoring proteins keep specific signalling proteins still scaffold proteins both bind signalling proteins together and keep them still
Intracellular signalling complexes many extracellular signal proteins can bind to the same receptor type and even activate same pathways this fact makes it more difficult to understand the specific responding of cells one explanation comes with signalling complexes that consist of several signalling proteins joined together these can be organized by scaffold proteins or temporarily around the phosphorylated cytoplasmic tail of the activated receptor or modified phospholipids of the plasma membrane