Cellular Communication and Signaling Dr. Mohammed Hussein M.B.Ch.B, MSC, PhD, MRCPCH, DCH (UK)

Cellular Communication and Signaling

Have you ever become separated from a friend while in a crowd Have you ever become separated from a friend while in a crowd? If so, you know the challenge of searching for someone when surrounded by thousands of other people. If you and your friend have cell phones, your chances of finding each other are good. A cell phone’s ability to send and receive messages makes it an ideal communication device.

Types of Signaling

Autocrine Direct Signaling Paracrine Endocrine

Autocrine Signaling

Autocrine Signaling Occurs during the early development of an organism to ensure that cells develop into the correct tissues and take on the proper function. Autocrine signaling also regulates pain sensation and inflammatory responses. If a cell is infected with a virus, the cell can signal itself to undergo programmed cell death, killing the virus in the process.

Autocrine Signaling In some cases, neighboring cells of the same type are also influenced by the released ligand. In embryological development, this process of stimulating a group of neighboring cells may help to direct the differentiation of identical cells into the same cell type, thus ensuring the proper developmental outcome.

Direct Signaling

Paracrine Signaling signals move by diffusion through the extracellular matrix elicit quick responses that last only a short period of time ligand* molecules are normally quickly degraded by enzymes or removed by neighboring cells Removing the signals will reestablish the concentration gradient for the signal, allowing them to quickly diffuse through the intracellular space if released again. example of paracrine signaling is the transfer of signals across synapses between nerve cells

Endocrine Signaling types of signals usually produce a slower response, but have a longer-lasting effect.

Cell Receptors Receptors are protein molecules in the target cell or on its surface that bind ligands.

Cell Receptors Internal Receptors (Intracellular) There are two types of receptors: Internal Receptors (Intracellular) Cell-surface Receptors (Transmembrane)

Internal Receptors Are found inside the cell (the cytoplasm or the nucleus) Respond to hydrophobic ligand molecules that are able to travel across the plasma membrane. Once inside the cell, many of these molecules bind to proteins that act as regulators of mRNA synthesis to mediate gene expression. Internal receptors can directly influence gene expression without having to pass the signal on to other receptors or messengers.

Cell Surface (Transmembrane) Receptors

Cell Surface Receptors Also known as transmembrane receptors, Are cell surface, membrane-anchored, or integral proteins that bind to external ligand molecules. Ligands that interact with cell-surface receptors do not have to enter the cell that they affect. Cell-surface receptors are also called cell-specific proteins or markers because they are specific to individual cell types.

Components of Cell Surface Receptors

Types of Cell Surface Receptors There are three general categories of cell-surface receptors Ion Channel-Linked Receptors Enzyme-Linked Receptors G-Protein-Linked Receptors

Ion Channel-Linked Receptors

enzyme-Linked Receptors

G PROTIEN-Linked Receptors

Signaling Molecules Signaling molecules are necessary for the coordination of cellular responses by serving as ligands and binding to cell receptors. Types of the Signaling Molecules Small Hydrophobic Ligands Water-Soluble Ligands Other Ligands

Small Hydrophobic Ligands Can directly diffuse through the plasma membrane and interact with internal receptors. Important members of this class of ligands are Steroid hormones, such as Female sex hormone, estradiol; Male sex hormone, testosterone; Cholesterol. Thyroid hormones Vitamin D. In order to be soluble in blood, hydrophobic ligands must bind to carrier proteins while they are being transported through the bloodstream.

Water-Soluble Ligands Are polar and, therefore, cannot pass through the plasma membrane unaided; sometimes, they are too large to pass through the membrane at all. Instead, most water-soluble ligands bind to the extracellular domain of cell-surface receptors. These water soluble ligands are quite diverse and include small molecules, peptides, and proteins.

Other Ligands Nitric oxide (NO) is a gas that also acts as a ligand. It is able to diffuse directly across the plasma membrane; One of its roles is to interact with receptors in smooth muscle and induce relaxation of the tissue. NO has a very short half-life; therefore, it only functions over short distances. Nitroglycerin, a treatment for heart disease, acts by triggering the release of NO, which causes blood vessels to dilate (expand), thus restoring blood flow to the heart.

Signal Transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellular response.

The Three Steps of Signal Transduction Reception Transduction  Response

Signalling Defects and Disease A large number of diseases are caused by defects in signalling pathways. The nature of these defects and how they are induced varies enormously. Pathogenic organisms and viruses, many of which can interfere with signalling events, cause some of these defects. .

Signalling Defects and Disease Most of the serious diseases in humans, such as hypertension, heart disease, diabetes and many forms of mental illness, seem to arise from subtle phenotypic modifications of signalling pathways. Such phenotypic remodeling alters the behavior of cells so that their normal functions are subverted, leading to disease.

Signalling Defects and Disease Phenotypic and/are genotypic modifications resulting from either somatic mutations or germline mutations have been proved to be the main cause of cancer development.

Signalling Defects and Disease Such modifications have been somewhat easier to diagnose, but have also proved difficult to treat as witnessed by the failure of many of the gene therapy strategies. Clearly, there is an urgent need to understand more about all of these disease states in order to design better therapies.

Signalling Defects and Disease The enormous redundancy built into cell signalling mechanisms offers many opportunities for discovering new ways of correcting many disease states.