UNIT 6 NOTES
I.
Communication Between Unicellular Organisms

Unicellular organisms gather information about their environment and respond to it appropriately by using signaling pathways -- part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The basis of this communication is releasing and accepting chemicals that trigger a set of actions inside the cell.

Cell communication in single celled organisms can be used o To relay information about food sources o Initiate sexual reproduction o Sense the number and type of cells nearby (quorum sensing) o Sense the location of favorable environment o Communicate other information between organisms

Example: Bacterial quorum sensing – Vibrio Harvey a marine bacterium emits light only if there is a high concentration of this bacterium present in the environment. The bacteria can do this by releasing a signal molecule. This signal molecule floats away in low concentration. However, in high concentration, it attaches to the membrane receptors of surrounding bacteria. The receptor activates genes to become active. The genes stimulate the production of proteins that will create bioluminescence.

The discovery of this process: http://media.hhmi.org/biointeractive/click/Quorum_Sensing/01.html

So the main components of the signal transduction pathway of this bacteria are: Signal molecule
– receptor – gene action – active proteins – bioluminescence

These processes are the main source of communication in multicellular organisms as well. Out nervous, endocrine and immune systems are all dependent on communication. Development is also based on it. There are thousands of processes in our body that follow the steps of cell signaling.


The basics of all cell communication: o Reception – a signal molecule or ligand binds to a receptor o Transduction – the intracellular part of the receptor activates a set of proteins and other molecules (signal transduction molecules) to send the message to various parts of the cell. o Response – the signal transduction molecules initiate a cascade that can lead to many different cellular actions such as turning genes on or off, stimulating protein formation etc.
II.
Types of Signal Molecules

Signal molecules or ligands are the molecules that come from the outside and binds with the receptors of the cells.

These signal molecules are organized according to distance that they travel to their target cells
(cells that have the proper receptors to take respond to the signal molecule):

Autocrine signals – signal molecules that have receptors on the cell that released them

Paracrine signals – the target cells with the appropriate receptors are near the cells that actually released the signal


Endocrine signals – hormones that are carried by the blood stream to distant cells to generate responses in those cells.
III.
Types of Receptors

A receptor on or in the target cell will be able to detect the signal molecule by matching
(complementary) shapes. So receptors are usually activated by molecules but may be activated by heat or light as well (photoreceptors in plants).

Ligand binding usually causes a receptor to undergo conformation (shape) change. This change usually directly activates the receptor to interact with other molecules inside the cell. In some instances receptor binding causes the aggregation of two or more receptors and causes further cellular changes.

Most receptors are protein molecules.
A.
Intracellular (Nuclear or Cytoplasmic) Receptors

Intracellular receptor proteins are found inside the cytoplasm or in the nucleus of the target cells. The signal molecules (ligands) in these cases must be able to pass through the cell

membrane to reach the receptor. Signal molecules can do this by being hydrophobic or small to cross the phospholipids bilayer. Examples of ligands that can pass through the cell membrane include steroids, thyroid, nitric oxide (NO).

The signal-receptor complex is able to regulate gene expression by acting as a transcription
factor that turns on specific genes. In cases of receptors that get into the nucleus, the receptor
 and ligand complex can carry out the entire reception and transduction process
Many of the intracellular receptor proteins have similar structures that suggest their common evolutionary origin.
B.
Receptors in The Plasma Membrane:

Water-soluble signal molecules bind to receptor molecules on the surface of the plasma membrane. These receptors have to change shape or aggregate to perform transduction.

Three major types of membrane receptors and their function: o G-protein-linked receptor: these receptors work with a G-protein (a group of proteins that are able to bind with and activated by GTP). The G-protein has two important binding sites. One site binds with the G protein-linked receptor, the other binds with
GDP in its inactive form and GTP, when the protein is activated. Many bacteria cause diseases by producing toxins that intervene with G-protein function. These receptors work the following way:
1.
The G-protein acts as a molecular switch which is either on or off, depending on which of the two guanine nucleotides is attached, GDP or GTP.
2.
When a matching signal molecule binds to the receptor molecule, the receptor is activated and changes shape. The change in shape activates the G-protein, so it replaces its GDP with a GTP.
3.
The activated G-protein dissociates from the receptor, moves to an enzyme and alters it.
When the enzyme is activated, it triggers a cellular response.
4.
The G protein changes back to its inactive form and returns to the receptor molecule. http://www.youtube.com/watch?v=bU4955rLv_8&feature=related

o Protein kinase receptors (receptor tyrosine kinase) – This group of receptors attach
ATP to tyrosine, an amino acid. These receptors, once they bind to two ligand molecules, form a dimer. The dimer formation pulls ATP molecules to the intracellular portion of the receptor and tyrosine molecules get phosphorylated. The phosphorylation will result in activating other inactive proteins intracellularly and generating a response. Good example of a protein kinase receptor is an insulin receptor in the target cells of the liver and muscles. Abnormal receptor tyrosine kinases that function in the absence of signal molecules can contribute to some kinds of cancer. http://www.youtube.com/watch?v=-iBb1sH-Eh4 o Ion channel receptors – a type of membrane receptors that can act as a gate when the receptor changes shape. When the signal molecule binds to the receptor protein, the gate opens or closes, allowing or blocking the transfer of specific ions such as Na + or
Ca 2+ . Each type of ion channel receptor has its ligand molecule (signal molecule) or another sensory signal such as light, sound, electric charge etc. (Ex. Acetylcholine receptors in nerve and muscle cells. These receptors open up when acetylcholine binds with them and allows Na + ions to rush into the cell to generate a nerve signal or contract a muscle).

IV.
Signal Transduction

Signal transduction pathways are a set of biochemical reactions that take place after a receptor is activated and results in a cell response.

Once these receptors are activated, one receptor can stimulate a cascade of one or multiple processes inside of the cell. These pathways can be highly complex.

The signaling pathway usually involves proteins. These proteins may not be active until activated by the receptor or they may be active until they are shut down by the activation of the receptor. The most common method of activating proteins is phosphorylation by ATP or other nucleotide triphosphates. The phosphate groups give two negative charges to the protein and modify its shape. As a result, the protein’s function is also modified.

After the protein performed its function, dephosphorylation modifies it back to its original shape by removing the phosphate groups by hydrolysis.

A large group of enzymes that perform phosphorylation of proteins are called kinases. They are specific to the proteins that they phosphorylate. Different enzymes are responsible for dephosphorylation. Phosphate groups can also be added to multiple sites on the protein so various levels of phosphorylation are possible.

Phosphorylation cascade occurs when numerous sequential proteins are phosphorylated and dephosphorylated one after the other.


Signal transduction pathways sometimes also require small, nonprotein molecules called second
messengers – these molecules mediate the signal from the receptor to the proteins. These second messengers usually modify the activity of enzymes that they bind with.

Important second messengers: o Cyclic AMP – An enzyme in the plasma membrane to convert ATP to cAMP in response to an extracellular signal (ex. Epinephrine). When the signal molecule binds to a receptor, the receptor activates this enzyme to form many molecules of cAMP. This way one signal molecule can induce the synthesis of many cAMP molecules. The cAMP molecule usually activates a protein kinase molecule to phosphorylate various proteins.
After this activation, the cAMP disintegrates. Many diseases are caused by toxins that interact with the second messenger system (ex. Cholera) o Ca 2+ ions – Many signal molecules, including neurotransmitters, growth factors, some hormones induce responses that increase the cytosolic concentration of calcium ions.
Increased calcium ion concentration can cause muscle contraction, secretion of certain substances or cell division. This system can work because the normal Ca 2+ ion concentration in the cytosol is a lot lower than in the smooth ER or in the extracellular matrix. A small change in the absolute concentration can result in a substantial change in the cytosol. A good example of Ca 2+ as a second messenger is when the sperm cell unites with the egg, results in a massive release of Ca ions into the egg cytoplasm that starts the various changes that leads to the development of the embryo.

o Nitric oxide (NO) – this very unstable gas that can act as a short term, short distance second messenger that is usually activated by Ca ions. NO generally result in muscle relaxation that is important when increased blood flow is required. (See our case study) o IP
3
is another second messenger that causes the release of other second messengers, like Ca 2+ .
V.
Cellular Responses

A single activated receptor can produce an exponential response due to signal amplification -- the binding of a signal molecule triggers successively larger responses along the transduction pathway.

A signal molecule eventually can stimulate a pathway into the nucleus and turn genes on or off.
They can do this by using transcription factors -- proteins that regulate RNA transcription from the DNA molecule. These transcription factors attach to the DNA at the promoter site (TATA box). If the transcription factor is an activator, it will stimulate transcription, if it is a repressor, it will prevent or slow transcription down. The transcription factors also get activated by phosphorylation.

Signal molecules can also open ion channels and stimulate transport of ions into or out of the cell (you will see this in nerve signaling). They can also facilitate cell movement or synthesis or breakdown of various organic molecules.

THE ENDOCRINE SYSTEM
I. Types of endocrine signaling

Endocrine signaling – endocrine cells release hormones that usually travel in the blood stream to the target cells. The network of hormone-secreting glands forms the endocrine system.

There is a hybrid of the nervous and endocrine system that combines and interacts with both the nervous and endocrine systems. This interaction is called neuroendocrine signaling – this pathway uses nerve cells that are located at the edge of blood vessels. They release neurohormones directly into the blood stream.

Neuroendocrine signaling makes the nervous and endocrine system an interconnected regulatory system.

Pheromones are a special group of signaling molecules that signal between organisms not within the same organism. These signals are released from the organisms into the air or water and can be used to communicate mating availability, food sources, danger or the borders of a territory. Pheromones can be species specific or colony specific.
II. Transmission of hormone signals

Hormones are long-distance signals that are released by endocrine cells and travel to the target cells in animals through the blood stream.

Hormones are used to alter existing cell functions, regulate homeostasis, enhance growth and development and regulate metabolism.

Lipid-soluble hormones can enter the target cell’s nuclei and directly regulate genes. These hormones cannot travel in the blood stream on their own, they need polar transport proteins to carry them.

While water-soluble hormones are not able to enter the cell membrane and must bind to membrane-receptors to initiate a cell signaling pathway. These hormones also need to be released by exocytosis because they cannot exit the cell membrane either.

The response to the hormone in the target cell depends on the type of receptors the hormones have on or in the target cells. Different receptor-hormone complexes can bind to different genes and initiate the production of different proteins. In the case of water-soluble hormones the response also depends on the type of cell signaling pathway that is initiated.
III. The Chemical Structure and Function of Hormones

Hormones are all organic molecules that can be classified chemically into three groups: o Amines – small organic molecules that contain amino groups Ex. Epinephrine, norepinephrine, thyroxine (T
4
), dopamine o Peptides or proteins – peptide is any compound that contains two or more amino acids combined by peptide bonds. Ex.: insulin, glucagon, oxytocin, o Steroids – made up of sterols. Ex. Cortisol, testosterone, estrogen

In general, amines and polypeptides are usually polar while sterols are nonpolar.
IV. The Interactions and Special Characteristics of the Nervous and Endocrine Systems

There are major differences between the nervous and endocrine systems: o The endocrine cells are not directly attached to the target cells that they regulate, so they can regulate cells in multiple locations, far away from each other and from the endocrine gland. However, nerve cells are directly attached to cells that they regulate.

 o Because the hormones of the endocrine system travel in blood vessels to long distances, this system generally is slower than neural signaling that carries the signal by electric impulses within less than a second from one side of the nerve cell to the next. o The endocrine system uses existing structures such as blood vessels for transmission while nerve cells have their own structures called synapses to transmit signals.
There are also many overlapping areas between the two systems. For example, neurosecretory
cells are nerve cells that release hormones. These cells receive signals from both the nervous and the endocrine systems and use those signals to release regulatory hormones. The hypothalamus is one example where a part of the nervous system releases several different hormones to directly control growth, development or child birth or to regulate other endocrine organs.
V. Basic Components of a Hormone Signaling Pathway

Hormones interact with the nervous system. We use our sensory organs for example to detect changes in the environment. These changes will be received and processed by the nervous system. For example to the hypothalamus. The hypothalamus can release hormones into the blood stream while also release nerve signals into the body. Than when the target cells get the signals from the hypothalamus and start their individual signal transduction pathways and responses. This way the one organ can generate multiple responses in different types of cells.

Example is the “fight or flight response”:

Hormones also interact with other tissues of the body. A stimulus triggers endocrine cells to release hormones. These hormones travel in the blood stream to the target cells. The target cells with the right kind of receptors take in the hormone and generate a cell signaling pathway in response. The response of the cell can change homeostasis, make the cell divide, change its metabolism….
VI.
Hormones and Homeostasis

Hormones actively participate in maintaining homeostasis by participating in positive or negative feedback mechanisms. Their production can also be regulated by these feedback mechanisms.


An example of a negative feedback mechanism is the regulation of thyroid hormone production.
Thyroid hormones, T
3
and T
4
have an effect on most cells in the body by regulating important processes such as metabolism, growth, development, heart rate, mental state, reproductive functions and vasodilation. Thyroid hormone release is tightly regulated by the hypothalamus by the following process: o Stimulus, such as the drop of temperature is detected by nerve cells in the hypothalamus. o The neurosecretory cells of the hypothalamus release a stimulating hormone called thyrotropin-releasing hormone (TRH), which travels to the anterior pituitary in the blood stream. o TRH stimulates the production of another stimulating hormone, called thyroidstimulating hormone (TSH). o TSH travels in the blood stream into the thyroid gland and stimulates the production and release of T
3
and T
4
. o T
3
and T
4
leave the thyroid gland and moves to the target cells in the blood stream.
There is a wide range of target cells with different receptors and very different responses. o Some of the thyroid hormones return to the hypothalamus and inhibit the production of more TRH and TSH hormones. This is a negative feedback mechanism, which is necessary to stop overproduction of all other hormones that are stimulated by TRH.

An example of positive feedback is observable during child birth with the effect of oxytocin hormone: o As labor progresses, the head of the fetus presses on the cervix. This pressure is a signal to the nervous system that stimulates the hypothalamus. o The hypothalamus produces and releases oxytocin into the pituitary gland. o The pituitary gland may store this hormone, it starts to gradually release it into the blood stream. o Target cells in the uterus detect this hormone and start muscle contractions. o These contractions push the fetus’s head even more to the cervix, so more hormone is produced and released. This hormone also stimulates milk gland cells to produce and release milk. o Hormone levels return to low later, well after birth.
VII.
When Hormone Regulation Fails

When hormone regulation fails, various disorders can occur. Some of them are debilitating or even deadly.

Example: The thyroid gland T
3
and T
4
production is too low (hypothyroidism), goiter forms from the enlargement of the thyroid gland. This condition is more serious if the hypothyroidism occurs in young age, short stunted growth, mental retardation can be the result. The overproduction of the thyroid gland is hyperthyroidism, can result in a different kind of goiter, very high metabolism, nervous temperament, high blood pressure, bulging eyes etc. Today, both conditions can be treated with medication and diet (iodine containing salt).

THE NERVOUS SYSTEM
I. The Division of the Nervous System

The nervous system is composed of two main parts: o Central nervous system (CNS) – includes the brain and the spinal cord o Peripheral nervous system (PNS) – nerves and nodes that form a network outside of the CNS and transmit messages into the CNS. A nerve is composed of the axons of nerve cells bundled together.

The basic unit of signal transmission in both the CNS and PNS is the neuron.
II. Cells of the Nervous System
A.
Neuron

We had the composition of the neuron before. Please review.

The myelin sheath of the nerve cell is made up of Schwann cells in the PNS and oligodendrocytes in the CNS. These cells serve as insulation over the axon. This insulation assures that only the exposed, in between sections (nodes of Ranvier) participate directly in the signal transmission, making the transmission process a lot faster.

However, not all neurons myelinated. The ones in the gray matter in the brain for example are not. These neurons are short, have close connections so speed for them is not so important.

The width of the axon also improves signal transmission. The thicker the axon is, the faster the conduction occurs because of the lower resistance of the thicker axon (Ohm’s law – physics).


There are three major types of neurons in the body based on the information that they transmit: o Sensory neurons – transmit information from the body toward the central nervous system o Motor neurons -- these transmit information from the central nervous system to the rest of the body o Interneurons – found only within the central nervous system. Connect various parts of the CNS to each other

Most neuronal pathways are composed of at least one of each of the neuron types: sensory neuron interneuron motor neuron. The shape of these neurons can vary as well.

Within the structure of the neuron, the dendrites or nerve cell body receive signals from the surroundings. This signal travels forward in the axon toward the axon terminals. The axon terminals connect the neuron to other cells and forward the signal to them.
B.
Glial Cells

Glial cells are the other type of important cells of the nervous system. These cells provide insulation, nourishment, regulation to the neurons. They help to regulate the contents of the extracellular fluid around the neurons. Schwann cells in the PNS and oligodendrocytes in the

CNS that form the myelin sheath are glial cells.
New research also suggests that glial cells are active in transmitting messages but this is not yet conformed.
III. Nervous System Diversity

Through the course of evolution, simple systems to detect environmental changes gradually changed into more sophisticated systems.

Among animals, cnidarians have the simplest nervous system called a nerve net – a network of interacting neurons.

From flatworms on, a gradual increase of the number of nerve cells occurs around the head.
This is called cephalization. The regulatory functions also get more concentrated in the brain of higher animals. This process is called centralization.


The activity and behavior of animals is usually also related to the complexity of the nervous system. Animals that are sessile (remain in one place) or slow moving with simple behaviors tends to have simple nervous system. While organisms that are fast moving and have complex behaviors and intricate senses have more advanced brains.
IV. Action Potential
