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Chapter 10

BIOL 1090 Chapter Notes - Chapter 10: Cell Membrane, Phosphate, Guanine

3 pages80 viewsFall 2013

Department
Biology
Course Code
BIOL 1090
Professor
Marc Coppolino
Chapter
10

Page:
of 3
Cell Signalling and Signal Transduction: Chapter 10
September-22-13
10:35 PM
Cell Signaling and Signal Transduction
-Extracellular messenger molecules communicate between cells
-Messengers can travel short distances and stimulate close cells, or they can travel through the body to
stimulate cells that are farther away
-Many different ways for cells to signal:
Autocrine Signalling occurs when the cell producing the messenger expresses receptors to respond to the
messenger
Paracrine signaling is more limited as they cannot travel as far and may be unstable
Endocrine signalling is when the messenger molecules reach target cells through the bloodstream. These
messengers are called hormones and they act on target cells
-Cells can only respond to extracellular messages if they have receptors that will recognize and bind to the
messenger molecule. The molecule that binds to the receptor is a ligand.
-Activities a cell engages in depends on stimuli as well as intracellular machinery.
-Two major routes of signalling for cells:
Type One: A receptor sends a signal to an enzyme which sends a secondary messenger which will activate
or inactivate specific proteins.
Type Two: Receptor will send a signal by transforming the cytoplasmic domain into a station for proteins to
interact with each other.
-Alterations to signaling proteins are often caused by protein kinases or phosphatases which add or remove
phosphate groups from proteins
-Protein phosphorylation changes protein behaviour by activating or inactivating an enzyme, increasing or
decreasing protein-protein interactions, inducing a protein to move from one compartment to another
initiating protein degradation.
Signal transduction is defined by the way information carried by extracellular messenger molecules is
translated into changes within a cell. Almost all activity a cell engages in is from signals originating on its
surface.
Extracellular Messengers
-Large variety of molecules can be carriers of information such as:
Amino acids and their derivatives: Neurotransmitters and hormones
Gases: NO, CO
Steroids: Made from cholesterol
Eicosanoids: non polar molecules from fatty acid which regulates pain, inflammation, blood clotting etc.
Polypeptides and proteins
-Receptors that mediate signal transduction are:
G-protein coupled receptors: Huge family containing trans membrane helices which activate GTP binding
proteins that are responsible for many processes.
Receptor protein tyrosine kinases
Ligand gated channels: Conduct flow of ions are membrane
Steroid hormone receptors: increases or decreases gene transcription rate
B and T Cell receptor: Involved in foreign antigen response
Apoptosis: Programmed Cell Death
-Orderly process
-Different from necrosis which is cell death by trauma or biochemical insult. Necrosis causes swelling of
cell and organelles, leaking of contents and inflammation.
-Apoptosis is involved in the elimination of cells that have genomic damage which is important as if
these cells are not eliminated, unregulated cell division and cancer may occur
-Caspases are activated early on in apoptosis and trigger most of the changes that cause cell death
Intrinsic pathway of apoptosis: Internal stimuli, such as genetic damage, lack of oxygen, high
concentrations of cytosolic calcium, infection, stress or severe oxidative stress can trigger apoptosis by
the intrinsic pathway.
-Regulated by the family of Bel-2 proteins
-BH3- only proteins are the determinants as to whether a cell will live or die. In a healthy cell, BH3-only
proteins are inhibited or absent.
-Death begins with the release of cytochrome c molecules from the mitochondria
-As apoptosis occurs, cells shrink and lose contact with their neighbours until they disintegrate into an
apoptotic body
-Phospholipid from inner leaflet of plasma membrane presents itself on the outer leaflet which signals
for macrophages to eat the dead cell, so cellular contents aren’t released as they can be in necrosis as
this can lead to inflammation
Endomembrane System
-Network where materials are shuttled from one part of the cell to another
-Many are transported between organelles in transport vesicles
-Vesicles are pulled through cytoplasm by tracks made by microtubules and microfilaments of
cytoskeleton
-At their destination, vesicles fuse with the membrane of the compartment that it was targeted for
Biosynthetic pathway: Occurs when proteins are synthesized in the ER, modified through the Golgi
complex and then transported to various destinations. Many of these proteins are destined to be
secreted from the cell.
Constitutive secretion is when materials are moved by vesicles and discharged in a continuous manner
Regulated secretion is when materials are stored in packages and discharged only when there is a
stimulus.
Endocytic pathway: Materials move from the outer surface to compartments. Opposite of biosynthetic
pathway
Insights gained from the use of the green fluorescent protein
-Protein emits green fluorescent light. Using this, DNA encoding this protein can be fused to DNA
encoding the protein to be studied which causes the light to be fused to the protein of interest to be
studied.
-This helps scientists to study the pathways of specific proteins within a cell
G Protein-Coupled Receptors and their Second Messengers
-GPCR's are the largest family of genes encoded by the human genome
-Many natural ligands bind to GPCR's
-G proteins are called this because they bind to guanine nucleotides, either GDP or GTP
-Heterotrimeric G proteins all consist of three polypeptide subunits (a, B, y) and are held at the membrane
by lipid chains
-When GTP is replaced by GDP after interacting with GPCR's, it causes a change within the subunit
-With GTP, the trimeric complex disassociates and are free to activate an effector protein which can lead to
the activation or production of a second messenger
-G proteins are considered ON when it’s A subunit is bound to GTP. It can turn itself off using hydrolysis to
convert GTP to GDP and inorganic phosphate.
-Desensitization, which blocks active receptors from continuing to turn on G proteins occurs in two
steps. First cytoplasmic domain is phosphorylated by a kinase called the G protein-coupled receptor
kinase. Then, arrestins (proteins) bind to GPCR's so the G proteins are deactivated.
-Desensitization is important so that the cell is able to respond to a changing environment as opposed to
firing endlessly.
-When all three subunits re-associate with each other, the system returns to a resting state

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