1. An Intermediate-Level Lesson on 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”.

2. Elementary Vocab Refresher
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.

3. 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.

4. Lesson Vocab, pt. I
Cell junctions: allow molecules to pass readily between adjacent cells w/o crossing the plasma membranes. Found in both animal & plant cells.
Cell-cell recognition: two animal cells may communicate by interaction from surface-bound receptor/agonists protruding from their surface.
Dimer: complex formed from two receptor monomers which are closely associated during transduction.

5. Lesson Vocab, pt. II
Transcription factors: proteins which control which genes are “activated” – transcribing them into mRNA. Very important regulatory mechanism.
Signal protein de/phosphorylation: very common cellular mechanism for regulating protein activity. Plays a critical role in receptor tyrosine kinase (RTK) dynamics.
Protein kinase: an enzyme that transfers PO43 - (this is the symbol for a phosphate group) from ATP to a protein. Very important in transduction for eukaryotes.
Often act on other protein kinases in a pathway (i.e. phosphorylation cascade).

6. The Three Stages of Cell Signaling
Reception: the detection of an incoming, extracellular signaling
molecule by the target cell. A chemical signal is generally “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 (ligand) 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, determined by the type of cell which the target receptor is located in/on. 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 that participate in transduction along 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.

7. 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.

8. Plasma Membrane Receptors
The plasma membrane is a permeable wall made of lipids and proteins which controls what is allowed in and out of a cell. Most receptor sites are located here.
Signals transmitted to these plasma membrane-bound receptors are passed from the extracellular environment to the inside of the cell by changing the physical shape of the receptor temporarily.
Ligands for plasma membrane-bound receptors are generally too large to pass through the plasma membrane. Some receptors are located within the cell itself, however, and require the ligand to enter the cell itself. Most signals are transduced through other mediums which are activated by the receptor.

9. 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.

10. 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.

11. 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.
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.

12. Synaptic Signaling: the Basics
Alternating chemical and 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.

13. 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!

14. 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.

15. G-protein coupled receptor (GPCR)
A cell-surface transmembrane receptor that works through a G-protein; which bind (energy-rich) GTP, and act as molecular switches depending on which of the two guanine nucleotides is attached
(GTP activates, GDP deactivates)
Used by epinephrine and other hormones, as well as by neurotransmitters among other types of ligands.
Make up a large family of eukaryotic receptor proteins with a secondary structure in which its single polypeptide chain is twisted into a shape creating various receptor sites. Despite this, they are remarkably similar in structure.

16. GPCR Diagram

17. Receptor Tyrosine Kinases (RTK)
Kinase: enzyme that catalyzes the transfer of phosphate groups.
Major class of plasma membrane receptors, characterized by enzymatic activity and the enabling of multiple, simultaneous transduction pathways.
The part of the receptor protein extending into the cytoplasm functions as a tyrosine kinase to catalyze the transfer of a PO43- group from ATP to the amino acid tyrosine on a substrate protein.
One RTK complex may activate 10 or more different transduction pathways/cell responses – often multiple at once, enabling multitasking in regulatory activity.

18. RTK Diagram
Fig.5 (above): this pictured structure is a very standard RTK receptor schematic. The binding of a ligand to these two, individual RTK monomer receptors have caused them to become fused into a complex known as a dimer, following which the RTK receptor complex will “steal” a PO43- from a nearby ATP molecule to activate itself through phosphorylation. This process will cause the pictured “activated” relay proteins within the cell to recognize the RTK complex receptor as requiring them to transduce the signal along the pathway, or even creating the cellular response directly through them.

19. Ligand-Gated Ion Channel Receptor
Ligand-gated ion channel: type of membrane receptor containing a region which acts as a “gate”, opening or closing a transmembrane pathway in response to specific ion ligands (e.g. Na+ or Ca2+).
Specific ions may flow through the channel/pathway, if the gate is open, and rapidly alter intracellular concentration of that respective ion, typically altering cell activity and producing a cellular response.
Critically important mechanic in the nervous system:
Neurotransmitters released at a synapse often bind as ion channel ligands, transforming a chemical signal into an electrical one.

20. Ligand-Gated Ion Channel Diagram
Fig.3 (left): when the correct molecule with the correct electrical charge binds to a compatible ion-gated receptor, the protein gate will shift its physical structure temporarily, in order to open or close the channel running through it - (usually) in order to allow other ions to flood into the cytosol of the cell to produce a cellular response. Sodium (Na+) and calcium (Ca2+) ions are critical components of signaling within the brain.
Fig.3 (above): extracellular environments are usually much higher in ion concentrations that the intracellular space. Ca2+ levels outside of cells are approx. x250,000 times those found within the cytosol of a human cell. Those ions brought into the cytosol are usually sent into the endoplasmic reticulum or mitochondria.

21. Steroid Hormone Signaling
Testosterone behavior makes for a good example; secreted by testes cells, travels through blood into cells all over the body – though only cells with testosterone receptors respond.
Testosterone receptor transduction allows the ligand to enter the nucleus and turn on specific male sex characteristic-genes through mRNA transcription.
Testosterone receptors act as transcription factors for the ligand, completing signal transduction. Most intracellular receptors function this way.
Many other hormone receptors, such as thyroid, are already in the nucleus before the signal reaches them.

22. Testosterone-Signaled mRNA Transcription Diagram
Fig.3 (right & above): testosterone is one of a relatively small number of ligands which, despite being large and/or complex molecules, are able to enter the interior of their target cell (by forming a ligand-receptor complex whose shape permits passage through the plasma membrane) in order to directly produce a cellular response. The figure to the right depicts testosterone controlling gene activation.

23. Plasma membrane-bound receptors usually have multistep transduction pathways - steps often include:
Activation of proteins by addition/removal of PO43-, and/or release of other small signaling molecules or ions.
Multistep transduction may possibly greatly amplify signals; such as through signaling multiple molecules, allowing for many activated molecules at the end of the pathway. This also provides more opportunities for coordination/regulation compared to simpler systems.
Multistep transduction is usually assisted by dedicated molecules known as scaffolding proteins, which

24. 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.

25. Protein Kinases: the Basics
Work by transferring PO43- from ATP to proteins, often activating each other in chain reactions during transduction.
May “activate” or decrease the function of a protein.
A single cell may have hundreds of different kinds, each for a specific substrate protein.
Different from RTK because of heterologous protein targets (no dimers).

26. Protein Phosphatases: the Basics
Enzymes that rapidly dephosphorylate proteins to inactivate protein kinases, enabling negative feedback mechanics after the signal is gone.
Also make protein kinases available for reuse.
Together, the two enzymes control the activity of all proteins that regulated by PO43- at any given moment.
Thus; critical to phosphorylation cascade mechanics.

27. Signaling Messengers
“First messenger”: the original, extracellular ligand to bind to a receptor.
Second messengers: small, non-protein, water-soluble molecules or ions. These can readily spread through a cell by diffusion, and participate in GPCR/RPK transduction pathways.
Two most widely used “2nd messengers” are cyclic AMP and calcium ions (Ca2+)

28. Cyclic AMP/cAMP
Relay molecule that broadcasts signals to the cytoplasm from a ligand/signaling molecule (usually a hormone). Converted from ATP.
Converted by the membrane-bound enzyme; adenylyl cyclase, from ATP into cAMP in response to signaling – often by a scaffolding protein in the transduction pathway which activates the enzyme, enabling rapid production of cAMP without the need for numerous, individual signals.
Immediate effect is usually the activation of a serine/threonine kinase called protein kinase A.
Converted into AMP by phosphodiesterase after a short interval of time, in the absence of its ligand-hormone.
cAMP production can be found in G-proteins, GPCRs, and protein kinases. Some G-protein systems inhibit adenylyl cyclase, thus impairing cAMP synthesis.