Cell Communication

Overview: The Cellular Internet
  • Cell-to-cell communication is absolutely essential for multicellular organisms. Cells must communicate to coordinate their activities.
  • Communication between cells is also important for many unicellular organisms.
  •  Biologists have discovered universal mechanisms of cellular regulation involving the same small set of cell-signaling mechanisms. o The ubiquity of these mechanisms provides additional evidence for the evolutionary relatedness of all life.
  • Cells most often communicate by chemical signals, although signals may also take other forms. 
Concept 11.1 External signals are converted to responses within the cell. 

  • One topic of cell “conversation” is sex.
  • The cells of Saccharomyces cerevisiae, the yeast of bread, wine, and beer, identify potential mates by chemical signaling.
  • There are two sexes, a and A, each of which secretes a specific signaling molecule, a factor and A factor, respectively. These factors each bind to receptor proteins on the other mating type. After the mating factors have bound to the receptors, the two cells grow toward each other and undergo other cellular changes.The two cells fuse, or mate, to form an a/A cell containing the genes of both cells. 
  • The process by which a signal on a cell’s surface is changed or transduced into a specific cellular response is a series of steps called a signal transduction pathway.
  • Cells may communicate by direct contact

  • Chemical messages which elicit a response in cells server as a form of communication between cells 
  • Found in all cells 
  • Extremely conserved (similar) in widely different organisms (such as humans and yeast) leads one to believe that this evolved very early in the history of life 
Local Communication
  • Used by cells to communicate to their immediate neighbors 
  • One cell secretes a signal molecule into the extracellular fluid which is picked up by the target cells 
  • One example of this is at the synapse of two neurons 
Long Distance Signaling
  • Hormonal Signaling in Plants and Animals 
  • Used by cells to communicate to other cells a great distance away (but still in the same organism) 
  • One cell secrets a signal molecule (hormone) into the blood system (if an animal) or into the extracellular fluid (if a plant) 
  • The signal molecules travels throughout the body, most likely contacting nearly all cells in the organism 
  • Only the target cells, however, will have the receptors necessary to elicit the response 
The Three Stages of Cell Signaling - Reception, Transduction, Response 

Reception 
  • A chemical message binds to a protein on the cell surface 
Transduction 
  • The binding of the signal molecule alters the receptor protein in some way. 
  • The signal usually starts a cascade of reactions known as a signal transduction pathway 
Response 
  • The transduction pathway finally triggers a response 
  • The responses can vary from turning on a gene, activating an enzyme, rearranging the cytoskeleton 
  • There is usually an amplification of the signal (one hormone can elicit the response of over 108 molecules 

Concept 11.2: Reception: A signal molecule ninds to a receptor protein,causing it to change shape

G-Protein-Linked Receptor Sequences
 
  • G-protein-linked receptor is bound to the plasma membrane. 
  • All G-protein-linked receptors have similar structure regardless of the organism in which they are found 
  • Seven alpha-helices integrate the G-protein-linked receptor to the membrane 
  • Signal-binding site on outside of cell 
  • G-protein-interacting site on inside of cell 
  • When signal molecules binds to G-protein-linked receptor, the receptor is activated 
  • Altered G-protein-linked receptor activates a nearby G-protein 
  • G-protein - molecule in signal transduction sequence which has a bound GDP (guanine diphosphate, a relative of ADP and ATP) 
  • The activation occurs when a GTP displaces the GDP bound to the the G-protein. 
  • The activated G-protein then binds to another protein, usually an enzyme, and alters its activity 
  • This activation is usually temporary as the activated G-protein soon hydrolyzes the terminal phosphate on the bound GTP, forming GDP, thereby deactivating the G-protein
  • .
  • The deactivated G-protein is available for reactivation if the G-protein-linked receptor becomes activated again 
  • All three molecules, the G-protein-linked receptor, the G-protein, and the target enzyme, remain bound to the plasma membrane 
  • G-protein signal transduction sequences are extremely common in animal systems 
  • embryonic development 
  • human vision and smell 
  • over 60% of all medications used today exert their effects by influencing G-protein pathways 


  • Tyrosine-Kinase Receptors - Another Example of a Signal Transduction Pathway 
  • Tyrosine-Kinase Receptors often have a structure similar to the diagram below: 
.

  • Part of the receptor on the cytoplasmic side serves as an enzyme which catalyzes the transfer of phosphate groups from ATP to the amino acid Tyrosine on a substrate protein 
  • The activation of a Tyrosine-Kinase Receptor occurs as follows: 
  • Two signal molecule binds to two nearby Tyrosine-Kinase Receptors, causing them to aggregate, forming a dimer 
  • The formation of a dimer activated the Tyrosine-Kinase portion of each polypeptide 
  • The activated Tyrosine-Kinases phosphorylate the Tyrosine residues on the protein 
  • The activated receptor protein is now recognized by specific relay proteins 
  • They bind to the phosphorylated tyrosines, which cause a conformation change. 
  • The activated relay protein can then trigger a cellular response 
  • One activated Tyrosine-Kinase dimer can activate over ten different relay proteins, each which triggers a different response 
  • The ability of one ligand binding event to elicit so many response pathways is a key difference between these receptors and G-protein-linked receptors (that, and the absence of G- proteins of course...) 
  • Abnormal Tyrosine-Kinases that aggregate without the binding of a ligand have been linked with some forms of cancer 
  • Signal Transduction Pathways are often complex, having many, many intermediates participating in the cascade.
 11.3 
transduction: cascades of ,molecular interactions relay signals from receptors to target molecules in the cell > 
- when signal receptors are plasma membrane proteins, the trasduction stage of the cell signaling is usually a multistep pathway .
- pathways provide more opportunities for coordination and regulation than simpler systems
- small numbers of extracellular signal molecules can produce a large cellular response 
signal transduction pathway
- signal transduction leads to a particular response within the cell 
-signal activated receptors, activates another protein, which activates another molecule 
- until the protein that produces the final cellular response is activated 
- sometimes the original signal molecule is not passed along a signaling pathway : in most cases it never enters the cell
protein phosphorylation and dephosphorylation
phosphory and dephosphorylation of protein is a: wild spread cellular mechanisms for regulating protein activity 
the general name for an enzyme that transfers phosphate groups from atp to a protein is protein kinase 

11.8
-this picture is " a phosphorylation cascade" . in a phosphorylation cascade, a series of different molecules in a pathway are phosphorylated on turn , each molecule adding a phosphate group to the next one in line. The inactive and active forms of each protein are represented by different shapes to remind you that activation associated with a change in molecular conformation.
- many of the relay molecules in signal transduction pathways are protein kinases and often action other protein kinases in the pathways .
- 2% of our genes are protein kinases
- a single cell can have hundreds of kinds, each specific for a different substrate protein 
-abnormal activity of such a kinases can cause abnormalance in growth and can cause cancer.
small molecules and ions as second messengers 

not all components of signal transduction pathways are protein which involve small, non protein called second messengers 
since second messengers are small they can spread rapidly throughout the cell by diffusion, the most widely used second messengers are CYCLIN AMP snd cslcium ions , ca2+. 
cyclin amp
the second messengers cyclin amp is made from atp by adenlyly, an enzyme embedded in the plasma membrane, cyclin amp Is inactivated by phosphodiesterase, an enzyme that converts to amp.
research has revealed that epinephrine is only one of my hormones and other signal molecules that triger the formation of cAMP. it has also brought to light the other components of cAMP pathways , including G proteins
G proteins linked receptors and protein kinases

11.4 
response : cell signaling leads to regulation of cytoplasmic activates or transcription

-how does signal transduction pathway lead to regulation?
. a signal transduction pathway leads to the regulation of one or more cellular activates. the response may occur in the cytoplasm or may involve action in the nucleus . 

11.3 shows the complete pathway leading to the release of glucose-1 phosphate from glycogen.
11.4 shows an example in which signaling pathway activates a transcription factor that turns a gene on : 
the response to the growth factor signal is the synthesis of mRNA, which will be translated in the cytoplasm into a specific protein. in other cases, the transcription factor might regulate a gene by turning it off, often a transcription  factor regulates several different gene.
signal amplification
the amplification effect stems from the fact that these proteins persist in the active form long enough to processes molecules of substrate before they become inactive again .



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