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There are four types of cell signaling:
1. Autocrine signaling is when a cell targets itself.

2. Juxtacrine signaling is when a cell targets a cell that it is connected to by gap junctions..

3. Paracrine signaling is when a cell targets a cell nearby.

4. Endocrine signaling is when a cell targets a cell that is far away and the signal has to travel through the bloodstream.

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STAGES OF THE SIGNAL TRANSDUCTION PATHWAY

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STAGES OF THE SIGNAL TRANSDUCTION PATHWAY

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The three stages of a signal transduction pathway are reception, transduction, and response. Reception starts with the detection of a signal molecule on a receptor  The signal is converted into a form that triggers a pathway that leads to a cellular response which is known as transduction. The response is a specific cellular response, which depends on what the signal is.

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A protein kinase add phosphate groups, which makes relay proteins active and allows them to carry signals.

A protein kinase cascade involves the phosphorylation of protein kinases. A protein kinase cascade works by taking a phosphate group from an ATP, which converts ATP to ADP, and connecting that phosphate group to a protein kinase. Every time a protein kinase is phosphorylated, the signal is amplified, which allows small signal to produce a large response.

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A ligand is a signaling molecule that binds to a receptor. It is usually smaller than the receptor itself. The ligand typically triggers cascades of molecules that lead to a cellular response

Cyclic AMP (cAMP) and calcium ions function as second messengers in signal transduction.

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A ligand binds to a G protein coupled receptor, which leads to a conformational change in that receptor. Once the conformational change occurs, the GDP that is connected to the G-protein is replaced with GTP and the G- protein breaks off from the receptor and binds to an enzyme on the plasma membrane. When the G-protein binds to the the enzyme, the enzyme becomes activated which triggers the activation of the second messenger. Once the second messenger is activated, the cellular response occurs. When the ligand leaves the receptor, the G protein will move back to the receptor and a phosphate will leave the G protein, converting the GTP back to GDP.

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The way the cell responds to a signal depends on the what the signal molecule is. For some cases, the response can be as simple as opening a channel. For other cases, the response can activate a gene to make a certain protein. There are many types of signals and responses and they can vary from simple to very complicated.

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Cockayne Syndrome is a rare form of dwarfism. It is an inherited disorder whose diagnosis depends on certain criteria:

1. abnormal growth, short stature

2. prematurely aged appearance

3. abnormal sensitivity to light

In the original form of CS, the symptoms get progressively worse and becomes obvious after the age of one year. An early onset of CS is noticeable at birth. There is also another type of CS, called Cockayne Syndrome Type III, that comes later in a child’s development and is generally a milder form of the disease.

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There are a total of 53 symptoms for CS. Some of symptoms are:

1. Severe growth deficiency

2. Slender nose

3. Joint limitation

4. Small pelvis

5. Delayed teeth eruption

6. Sunken eyes

7. Mental deficiency

8. Small head

9. Seizures

10. Photosensitive dermatitis

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Cockayne Syndrome, also known as CS, is an autosomal recessive disorder. There are four types of CS, however they are all very similar. CS can result from mutations in either the ERCC6 gene or the ERCC8 gene. These genes provide instructions for making proteins that are involved in repairing damaged DNA. This allows for damaged DNA to replicate leading to problems in the body. People who have this disease have the appearance of short stature and premature aging. They suffer through many symptoms, including growth failure and sensitivity to the sun.

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CS is extremely rare, less than 0.001% of people in the world inherit this disease. A person with CS will rarely live to be adults, in fact the average lifespan is 12.5 years.

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Currently, there is no specific treatment to cure CS. Patients should be treated based on the symptoms that they have. Physical, speech, vision, and hearing therapy is often beneficial for CS.

There is currently a lot of research being done for CS. Research centers in America and Germany are doing extensive research about CS and how it can be treated. The researchers are trying to figure out exactly why mutations are occurring in the ERCC6 and ERCC8 genes. Not many drugs are being used for treatments because the researchers believe that it will have a negative impact on the patient’s enzymes.

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TCR activates DNA replication, which is the process of DNA strands being copied by a complementary base-pairing into a compatible DNA sequence.

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The cell signaling pathway used in Cockayne Syndrome is transcription-coupled repair (TCR). TCR is the process of lesions being removed from strands of DNA.

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Mutations in the ERCC6 (CSB) and ERCC8 (CSA) genes cause Cockayne Syndrome. The ERCC6 and ERCC8 genes provide instructions for making two proteins, called CSB and CSA, which are involved in repairing DNA. If either gene is damaged, damaged DNA is not able to be repaired. As a result, damaged DNA accumulates, which can leads to impaired cell functions and eventually, cell death.  Increased cell death likely contributes to features of Cockayne Syndrome such as growth failure and premature aging.

The problem that causes CS is improper nucleotide excision. The damaged DNA is not cut out and replaced, therefore defective DNA is replicated. This causes problems in transcription that leads to defective mRNA and defective RNAs being produced. As results, apoptosis or abnormal cell division occur.

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“Cockayne Syndrome.” Genetic and Rare Diseases Information Center, U.S. Department of Health and Human Services

“Cockayne Syndrome - Genetics Home Reference.” U.S. National Library of Medicine, National Institutes of Health

“Genetics of Cockayne Syndrome.” Background, Pathophysiology, Epidemiology, 6 Jan. 2017