An Introductory Lesson to Cell Communication Fig.1 (above): Three basic mechanisms through which the body can regulate itself via chemical and/or electrical signals as a means of issuing commands and feedback. Fig.2 (right): chemical signals are only capable of being acted upon if the physical structure of the signaling molecule, or ligand, can fit into the frame of the receptor site. This functions very similarly to a lock-and-key. The ligand “unlocks” the transductive properties of the receptor “lock”.

Elementary Vocab, pt. I Signal: a chemical and/or electrical “message” sent between cells in order to produce a specific effect within the body. As you read this, many signals are being sent back and forth between cells in your eyes and nerve cells in various regions of your brain! Ligand: the signaling molecule (usually a chemical molecule, though ligands take many forms) which binds to a receptor in order to produce a desired cellular response. Receptor: a protein contained on/within the membrane of a specific cell, designed for a specifically shaped or charged ligand in order to transmit a regulatory command elsewhere in the body.

Elementary Vocab Refresher, pt. II Phosphate group (PO43-): one of the basic functional groups within chemistry that produces characteristic reactions, and often form building blocks of complex molecules. This is important in this context because of the role PO43- groups play in altering protein function. Neurotransmitter: chemical signaling molecules; usually found within vesicles inside of a synapse structure - they are released as a critically important means of communication within the brain, capable of producing a very wide variety of neurological effects. These are why you enjoy life. Hormone: chemical signaling molecules; typically (though not always) found within endocrine glands. These are released directly into the bloodstream and flood the body, though they are only able to signal a limited number of available receptors, depending on the particular hormone and many other factors. Typically used to maintain the natural balance of metabolism and chemical balance within the body (homeostasis). [Epinephrine = American term for Adrenalin] Molecular Complex: Integrated molecule consisting of two or more clearly identifiable components that have combined to carry out a function. Enzyme- substrate, DNA-histone protein, and ligand-receptor complexes are all common examples which are necessary for human life.

The Three Stages of Cell Signaling Reception: the detection of an incoming, extracellular signaling molecule by the target cell. A chemical signal is “detected” when the signaling molecule binds to a receptor protein located at the cell's surface or inside the cell. Transduction: the binding of the signaling molecule changes the receptor protein in some way, initiating the process of transduction. The transduction stage converts the signal to a form that can bring about a specific cellular response. Transduction sometimes occurs in a single step, but more often requires a sequence of changes in a series of different molecules – a signal transduction pathway. The molecules in the pathway are often called relay molecules. Response: the triggering of a specific cellular response by the transduced signal. The response may be almost any imaginable cellular activity – such as catalysis by an enzyme, activation of specific genes in the nucleus, or the release of neurotransmitters contained within synaptic vesicles (membrane sacs).

Ligand-Receptor Dynamics Ligand binding causes a receptor protein to change shape, initiating transduction. This leads to the end result, called the cellular response. Ligand concentration outside the cell determines how often a ligand is bound and causes signaling.

The Signal Transduction Process During transduction, the original signaling molecule is generally not physically passed along the signaling pathway – in most cases, it never even enters the cell. Chemical/electrical information – the signal – is passed from the ligand to the end of the signaling pathway by “relay molecules” to produce the response, during which the signal changes into a different form (usually a shape change in a protein, often phosphorylation) as it passes through the pathway.

Illustrated Summary of Basic Signaling Mechanisms Fig.X (below left and right): Gap junctions allow transmembrane permeation without the need for receptor-ligand complexes to allow passage. Fig.X (above): Detailed diagram of synaptic signaling. Fig.X (above): Simplified diagram of endocrine signaling. Fig.X (below): Simplified diagram of paracrine signaling. Fig.X (below): Cell-cell recognition. Signaling occurs with surface contact.

Local Signaling – Paracrine Signaling Diagram 1). Signaling molecule (typically a local regulating agent, such as a growth factor which adjusts the rate of certain types of biological processes in the area) is secreted en masse from a special vesicle (membrane sac) into the extracellular fluid, where it will make physical contact with the target cell and begin transduction. Fig.X (below): Target cell, receives regulatory signals Fig.X (below): Target cell, receives regulatory signals 2). The regulatory signaling molecule binds to receptors on the nearby target cells, often in high volumes. The regulatory signals are transduced, and the cellular response is produced. Fig. X (above, right, below): [Secretory vesicles]: ligands released from here. Fig.X (below): Target cell, receives regulatory signals Fig.X (above): regulatory signaling molecules indiscriminately released into the nearby extracellular fluid.

Paracrine Signaling: the Basics Designed to only affect nearby cells. Ligands are released indiscriminately into the surrounding extracellular fluid, rather than directly aimed towards a specific cell in the body. Metabolism and other biological processes may be regulated in a very specialized region, and in a time-effective manner, through paracrine secretion.

Local/Long-Distance Signaling – Synaptic Signaling Diagram Synaptic signaling only occurs between a nerve cell and a constituent cell of the nervous system such as a muscle cell or another neuron. Drugs produce mood- altering effects primarily through specific types of synaptic signaling aimed at various, specialized receptors. 1). An electrical signal travels down the length of the nerve cell and triggers the release of chemical neurotransmitters in order to transmit across the synaptic gap from the presynaptic neuron within the transduction pathway. 2). Neurotransmitters diffuse across the synapse, binding to postsynaptic receptor sites designed for them. The signal is passed on from this postsynaptic neuron as an electrical signal to the next synapse, after which the signal form will change back and forth once again. 3). The target cell is stimulated and initiates a response. This will most often simply be to send the signal further down the transduction pathway, though it can be many different things.

Synaptic Signaling: the Basics Alternating chemical and/or electrical signals travel the length of a nerve cell and are carried along a specific route, being converted between the two mediums as they move through various parts/structures of the transduction pathway in the nervous system. Primary means by which the brain is able to conduct cognition and influence emotional state. Signaling through the nervous system is usually considered short-distance, but can be considered long-distance as well.

Long-Distance Signaling – Endocrine Signaling Diagram Fig.3 (below): hormones are unique in their signal delivery system. By using the bloodstream as a means of transport, they are able to reach virtually every single cell in the body. Receptor sites designed for specific hormones can be found in a very wide variety of locations, though each generally have a distinctly different function from one another, despite being activated by the same ligand. The type of cell the receptor is a part of determines the cellular response produced. Fig.4 (above): hormones are singularly versatile as signaling molecules. Epinephrine receptors in the liver stimulate the breakdown of the carbohydrate glycogen, while those in the heart primarily exist to induce muscle contraction – raising the heart rate. Additionally, many can act as neurotransmitters. The burst of energy one experiences in moments in which a person feels mortally threatened is in part due to epinephrine signaling through receptors in the brain!

Long-Distance Signaling – Endocrine (Hormonal) Signaling Uniquely versatile in the roles they can fill – often able to work on peripheral nervous system receptors, as well as those in central nervous system – involving them in everything from the most minor movement to surprising aspects of perception and cognition Many hormones play critical roles as both neurotransmitters within the brain, and in more “traditional” PNS-regulating roles; involving everything from breathing and walking, to activating genes within your DNA genome.