mod 9 chap 9 Flashcards
Principles of cell signaling
the activties of all cells are infleuced by their surroundings
cells receive large amounts of info form diff sources in the surroundings
one key source of info is the phsyical enrvinment and anotehr is other cells
both unicellular and mulkticelular organisns sense info from their surroundings and repsond to that info by changing their atcivty ore even dividing
signaling mchencaisms evolved first in unicellular organisms as a way to sense and repsond to their envriment and as a way to ifnleucne the behaviour and acitvy of other cells
the genral princple of cell communicatoon apply to all cells, both proakryotic and eukaryotic and to all organisms
Cells communicate using chem signals that bind to receptors
cellular communication consists of four elements: signaling cell, signaling moelcule, recpetor protein and responding cell
the signaling cell is the sourve of a signlaing moelcule
signaling molecules may vary immensly and include peptides, lipids and gases
in all cases, the signaling moelcule carries info from one cell to the next
the siganling moelcule binds to a recptor protein on or in the responding cell; in turn the repsonding cell chneges its activty or behaviour
signaling moelcules are sometimes called signals and receptor proteins are called receptors
ex: You’re startled or scared, and you experience a strange feeling in the pit of your stomach and your heart beats faster. Collectively, these physiological changes are known as the fight-or-flight response. For these changes to occur, a signaling molecule must travel from signaling cells to responding cells in the heart, lungs, stomach, and many other organs (Fig. 9.2). The signaling molecule is the hormone adrenaline (also called epinephrine). In response to stress, adrenaline is released from the adrenal glands, located above the kidneys. Adrenaline circulates through the body and acts on many types of cells, including the cells of your heart, causing it to beat more strongly and quickly. As a result, the heart is able to deliver oxygen more effectively to the body. In this case, the signaling cells are specific cells within the adrenal glands. The signaling molecule is the hormone adrenaline released by these cells. Adrenaline is carried in the bloodstream and binds to receptor proteins located on the surface of responding cells, like those of the heart.
ex: Streptococcus pneumoniae (also known as pneumococcus) is a bacterium that causes pneumonia, meningitis, and some kinds of arthritis. Many bacteria, including pneumococci, are able to take up DNA from the environment and incorporate it into their genome (Chapter 24). By this means, individual bacterial cells can acquire genes with advantageous properties to the bacterium, including antibiotic resistance. n the 1960s, it was observed that the rate of DNA uptake by pneumococcal cells increased sharply once the bacterial population reached a certain density. Scientists concluded that the bacteria were able to coordinate DNA uptake across the population so that DNA uptake occurred only at high bacterial population density. It turns out that they are able to communicate this information to one another through the release of a small peptide. In the 1990s, scientists discovered a short peptide consisting of 17 amino acids that is continuously synthesized and released by pneumococcal cells. Not long after, a receptor for this peptide was discovered on the surface of these pneumococcal cells. The binding of this peptide to its receptor causes a bacterium to express the genes required for DNA uptake. When the bacteria are present at a low density, the peptide is at too low a concentration to bind to receptors on the bacteria (Fig. 9.3a). As the population density of the bacteria increases, so does the concentration of the peptide, until it reaches a level high enough that the peptide binds to receptors to cause the bacteria to turn on genes necessary for DNA uptake
in pneumoscuss we see an exmaple of quorum sensing, a pricess used by bacteria and other organisms to detect populatoion density and respond by turning on specific genes across the entire community
quorom sensing is used to controll and coordinate many diff types of bacterial behavours in addition to DNA uptake like antibitic production and biofilm formation
Quorum sensing by pneumococcus also illustrates the four essential elements involved in communication between cells. Each bacterial cell is both a signaling cell and a responding cell because each bacterial cell releases signaling molecules and binds signaling molecules on receptor proteins. The general idea that cells communicate by sending a signaling molecule that binds to a receptor on a responding cell is universal among prokaryotes and eukaryotes. The four essential elements—signaling cell, signaling molecule, receptor protein, and responding cell—act in very much the same way in myriad types of cellular communication
Signaling involves receptor activation, signal tranduction, response and termination
when a signal moelcule bnds to recptor:
the first step is recpetor actviation
on binding the signaling moelcule, the recpetor is turned on or activted
the signaling moelcule usually actviates the recptor by causing a conformational change in the recpetor
as a result of binding the signaling moelcule, some recptors bind to and actviate other poteins located inside the cell
otehr receptors are enzymes and binding of a signaling moelcule changes the shape and atcivty of the enzyme
still otehr recpetors are channels in the cell memrbane tha open or close in repsosne to teh bidning of a signaling moelcule
once actviated the receptor often triggers a series of downstream events in a process called signal transduction
during trasnduction, one moelcule actviates the next which goes on and on
tranduction can be thought of a chain rxn or cascade of biochem events set off by the bidnng and actviation of the receptor
imprtant aspect of signal tarnsudtcion is that the signal is often amplfiied at each setp (low signal conc can have a large effect on teh responding cell)
next there is a cellular repsonse which can take diff forms dpeneidng on the natrue of the siganling moelcule and the type of responding cell
ex. signaling pathways can actviate enzymes involved in metabolic pathwasy or turn on genes that cause the cell to divide, change shpa eor signal other cells
last step is terminaton in which the cellular rsponse is stopped
the cellular response an be terminated at any point along the pathway
temriantion protects the cell from overeacting to eixtsing signals therby holding the cellular response to an appropiate level
termination also frees up the cell to allow it to respond to new signals
In pneumococcal cells, for example, the peptide binds to and activates a receptor on the cell surface. When enough receptors are bound by the signaling molecule, the message is relayed by signal transduction pathways to the nucleoid. There, genes are turned on that express proteins involved in DNA uptake from the environment. Eventually, when the density of bacteria is low, the initiating signal falls below a critical threshold and gene expression is turned back off.
The response of a cell to a isgnaling molecule depnds on the type of cell
cells are typically exposed to many diff types of signalling moelcules
a cell responds to a signal only if it has recpetors that are able to bind to the signaling moelcule
if specific recptors are rpesent, binding of a signaling moelcule leads to downstream effects; if specific recpetors not rpesnet the cell cant respond
when a isgnaling moelcule binds to recpetor what determins the repsonse of teh cell
the cells response depends on the set of proteins the in the cell and the signaling pathways withn the cell as the diff cell types have diff sets of intracelular proteins and isgnaling pathways
as a result, the same isgnaling moelcuel can have diff effects in diff cells
ex. adrenline causes heart muscle clels to contarct quickly whereas it causes cells lining the airways of the lung to relax
Distance Between Cells
in prokartotes and unciellulr eukaryotes cell communication occurs between organisms
in compelx multicellular organisms, cell communication occurs between cells within teh same organism
the same princple of cell communication apply in both instances though there are differences
in multcellular organisms, the idstance between communciating cells will vary - when they are far apart, the signaling moelcule is trasnprted by circulatory ssustem - when they are close the signaling moelcule simply moves by diffsuion
in addition many cells in mutlicellualr organisms are phsycially atracted to one another in whcihc ase teh signaling moelcule isnt released from the signalling cell at all
Endocrine signaling acts over long distances
Signaling moelcules released by a cell may have to travel great distances to reach receptor cells in the body
in such cases they are often caried in teh circulatory system
signalling by means of molecules that travel through the blodosteram is called endocrine signalling
Adrenaline, discussed earlier, provides a good example of endocrine signaling. Adrenaline is produced in the adrenal glands and then carried by the bloodstream to target cells that are far from the signaling cells. Other examples of endocrine signaling involve the mammalian steroid hormones estradiol (an estrogen) and testosterone (an androgen). These hormones travel from the ovaries and the testes, respectively (although there are other minor sources of these hormones), through the bloodstream, to target cells in various tissues throughout the body. The increased amount of estrogen in girls during puberty causes the development of breast tissue and the beginning of menstrual cycles. The increased amount of testosterone in boys during puberty causes the growth of muscle cells, deepening of the voice, and growth of facial hair
signaling can occur over short distances
signalling can also occur between two cells that are close to each other
in this case, movement of teh signaling moelcule through teh circulatory system isnt needed
instead, the signaling moelcule can simpkly move by diffusion between the two cells
this form of signaling is called paracrine signaling
paracrine signalling moelcules travel distances aprox 20 cell diameteres or few hundred micrometers
in paracrine siganlling, the signal usually takes the form of a small water soluble moelcule such as a growth factor
a growth factor is a type of signaling moelcule that causes teh responding cell to grow, divide or differntiate
one of first growth factors disoverd was found by sicnetists attempting to udnerstand how to maintain cultures of cells in the lab
for decades research has worked iwth cells in cultures
intially these cultruee cells had limited use becuase they failed to divide outside the body unless they were supplied with unidenfiied factors from mamalian blood serum
in 19974 Kohler and lipton disovered that one of these fatcors is scerted by platelets leading it to be named platelt derived growth factor
we now know of scores of moelcules secreted by cells that function as growth factors; in most cases, the effects of rgowth factors are confied to the neighboruing cells
growth factors secreted by cells in embryo work over short distances to ifneluce the kind of cells their enighbours will become
in this way they help shape the strcuture of the adults tissues, organs and limbs
ex, in devertbrates, paracrine signlaling by the growth factor Sonic Hedgehog ensure that motor neurons inthe spinal cord are in the proper location, that yhe bones of your vertbral colum form correctly and that your thumb and pinky fingers are on teh correct sides of your hands
a specilized orm of short range signalling is the communcition between neurons and between neurons and muscle cells
neurontransmtters are a type fo signaling moelcule released from a neruon
after release they diffuse across small space called synapse, between signalling cell and repsnding cell
if the adjacent cell is a neuron then it responds by transmitting a nerve impulse and tehn releasing additional neurotransmitters
if repsoddng cell is a muscle cell it might respond by contracting
sometimes signaling moelcules may be released by a cell and then bind to recptors on the same cell
such cases where siganlling cell and repsdng cell are one and the same, are exmaples of autocrine signalling
autocrine signalling is imprtant to multicellualr organisms during dveeloment of embryo
ex. once a cell differtates ino a psecialized cell type, autcorine siganling is soemtimes used to maintain this dvelopmetal decision
signalling can cocur by direct cell to cell contact
sometimes a cell communciates with another cell through direct contact without diffsuion or circulation of the signaling moelcule
bc this form of isgnalling requires that the two comncating cells be in phsycal conatc with each otehr its called contac dependeet signalling
in this form, a transmemrbnae protein on surface of one cell acts as the signaling moelcule and transmenvrane protein on teh surace of adjcent cell acts as the receptor
as a result the signaling moelcule isnt released form the cell but remians asocited with the cell membrane
contact dependent signaling is imprtant during the dvelopment of the cenyal nervous system of vertebrate aniamsl
in teh brain and spinal cords, there are neruons that transmit info in the form of elictracl signals and glial cells, which noruish and insluate the neurons
both neurons and glial cells start out as similar undifferntaed cells in the embryo but some of these cells become neurons and many more become glial cells
During brain development, the amount of a transmembrane protein called Delta dramatically increases on the surface of some of these undifferentiated cells. These cells will become neurons. Delta proteins on each new neuron bind to transmembrane proteins called Notch on the surface of adjacent, undifferentiated cells. In this case, the signaling cell is the cell with elevated levels of Delta protein. The Delta protein, in turn, is the signaling molecule, and Notch is its receptor. Cells with activated Notch receptors become glial cells. Because one signaling cell sends this same message to all the cells it contacts, there are many more glial cells than neurons in the central nervous system.
As you can see, the same fundamental principles of cell communication are at work when signaling guides a developing embryo, allows neurons to communicate with other neurons or muscles, triggers DNA uptake by pneumococcal cells, or allows your body to respond to stress. These and many other examples of cell communication are all based on signaling molecules from a signaling cell that bind to receptor proteins in or on a responding cell. Signaling molecules are the language of cellular communication
Signaling Receptors
receptor are proteins that receive and interpet info carried by signalling molecules
regardless of distance between communciating cells, a respnding cell receives a message when the siganling moelcule binds to a recpetor protein on or in the cell
for this reason, the signaling moelcule is often refefred to as a ligand
the signalling moelcule binds to specific part of the recptor protein called the ligand binding site
the bond formed is noncovalent and highly specific: the siganling moelcule binds only to a recptor with a lignad binding site that reocgnizes the molecule
the binding of a signaling moecle to the ligand binding site of a receptor typcially causes a confomational change in teh receptor
the change actviates teh receptor bc it is through the change tha the receptor passes the message from the siganling moelcule to the inetrior of teh cell
the change in a recpetor ultemly yriggers chem rxns or other changes in teh cytosol so it serves as crucial step in the recpetion and interpettaion of communictaions from other cells
receptors for polar isgnaling moelcules are loctaed on the cell surface
the location of a particular receptor in a cell dpeends on hwetehr the signaling moelcule is polar or nonpolar
many signaling moelcules like growth factor are polar and cant pass through the cell membrane
the receptor proteins for these signals are lcoated on outside surface of the repsonding cell
recpetor proteins for growth factors and othe rpolar ligands are transmembrane proteins with extracellular domain, a trasnmemrbane domain and a cytosplasmic domain
when a signaling mellce binds to the ligand biding iste in the extracellular domain, the entrie moelcul, undergoes conformational change and as a result teh moelcue is activated
the receptor acts as a bridge between the inside and teh outside of the repsing cell that carries the message of the hyrophilic signal across teh hdyrphobic core of the cellk memrbane
Receptors for nonpolar signalling moelcules are located in inetrior fo teh cell
The receptors for nonpolar signaling molecules, such as the steroid hormones involved in endocrine signaling, are not located on the surface of the cell but are found inside the cell. Because steroids are hydrophobic, they pass easily through the hydrophobic core of the phospholipid bilayer and into the target cell. Once inside, steroid hormones bind to receptor proteins located in the cytosol or in the nucleus to form receptor–steroid complexes (Fig. 9.7b). Steroid–receptor complexes formed in the cytosol enter the nucleus, where they act to control the expression of specific genes. Steroid receptors located in the nucleus are often already bound to DNA and need only to bind to their steroid counterpart to turn on gene expression.
Many examples of steroid hormones exist, including sex hormones, glucocorticoids (which raise blood glucose levels), and ecdysone (involved in insect molting). However, because much of the information received by cells is transmitted across the cell membrane through transmembrane receptors, we focus our attention here on the sequence of events that takes place when receptors on the surface of cells bind their ligands
Cell surface recpetors act like moelcular switches
As we saw earlier, a receptor is activated after a signaling molecule binds to its ligand-binding site. Many receptors act as binary molecular switches, existing in two alternative states, either on or off (Fig. 9.8). In this way, receptors behave similarly to a light switch (Fig. 9.8a). When bound to their signaling molecule, the molecular switch is turned on. When the signaling molecule is no longer bound, the switch is turned off.
Thousands of different receptor proteins are present on the surface of any given cell. Most of them can be placed into one of three groups on the basis of their structures and what occurs immediately after the receptor binds its ligand.
One type of cell-surface receptor is called a G protein-coupled receptor (Fig. 9.8b and section 9.4). When a ligand binds to a G protein-coupled receptor, the receptor couples to, or associates with, a G protein, as its name suggests. G protein-coupled receptors are evolutionary conserved, and all have a similar molecular structure.
A second group of cell-surface receptors are themselves enzymes, which become catalytically active when the receptor binds its ligand. Most of these are receptor kinases (Fig. 9.8c and section 9.5). A kinase is an enzyme that catalyzes the transfer of a phosphate group from ATP to a substrate. To catalyze this reaction, it binds both ATP and the substrate in a process called phosphorylation (Fig. 9.9). Phosphorylation is important because it alters the activity of the substrate: when a protein is phosphorylated by a kinase, it typically becomes active and is switched on. The addition of a phosphate group can activate a protein by altering its shape or providing a new site for other proteins to bind. Phosphatases remove a phosphate group, a process called dephosphorylation (Fig. 9.9). When a protein is dephosphorylated by a phosphatase, it typically becomes inactive and is switched off.
Receptors in the third group, ion channels, alter the flow of ions across the cell membrane. Recall from Chapter 3 that channel proteins help ions and other molecules diffuse into and out of the cell by providing a hydrophilic pathway through the hydrophobic core of the cell membrane. Most of the time, the channels are closed. However, when a signal arrives, the channel undergoes a conformational change that opens it and allows ions to flow in and out. These channels can be opened in different ways. Some open in response to changes in voltage across the membrane; these are called voltage-gated ion channels and are discussed in Chapter 35. Other ion channels open when bound by their ligand; these are called ligand-gated ion channels (Fig. 9.8d) and are discussed in Chapter 36. Signaling using ion channel receptors is especially important for nerve and muscle cells because their functions depend on a rapid change in ion flow across the cell membrane
What happens after a signaling molecule binds to its receptor and flips a molecular switch? Following receptor activation, signaling pathways transmit the signal to targets in the interior of the cell, the cell responds, and eventually the signal is terminated. In the next two sections, we examine the signaling pathways activated by G protein-coupled receptors and receptor kinases.
G protein coupled receptors
G coupled receptors are a very large family of cell surface molecules
they are found in almost eevry eukaryotic organism
all of therese receptors have three charachterics in comon
first they have a similar structure, consisting of a single polypeptide chain that has seven transmemrbane spanning regions, with the ligand binding site on the outside of the cell and the portion that binds to the G protein on the inside of the cell
second when actviated they assicate with a G proteon - this way they are able to transmit a signal from the outside to the inside of the cell
third the cellular responses to the activation of G proein coupled recpetros all tend to be rapid and short lived
these comon charcterics result from their shared evolutionary histroy
In spite of their similarity, different G protein-coupled receptors are able to respond to different signaling molecules. Hormones, neurotransmitters, and small molecules are among the diverse set of signaling molecules that bind to this group of receptors. In addition, the effects of these receptors are quite diverse. For example, signaling through these receptors is responsible for our senses of sight, smell, and taste (Chapter 35). In fact, it is thought that G protein-coupled receptors evolved from sensory receptors in unicellular eukaryotes.
The first step in cell signaling is recptor actviation
A G protein-coupled receptor can be inactive (off) or active (on) depending on whether it is bound to a ligand. In the absence of a ligand, it is inactive. When a ligand binds to a G protein-coupled receptor, the receptor is active. In its active state, the receptor couples to (that is, it binds to) a G protein located on the cytoplasmic side of the cell membrane.
The G protein also has two states, off or on. A G protein is able to bind to the guanine nucleotides GDP (guanosine diphosphate) and GTP (guanosine triphosphate). When the G protein is bound to GDP, it is off, or inactive; when the G protein is bound to GTP, it is on, or active.
When a G protein-coupled receptor binds to a G protein, it activates the G protein by causing it to release GDP and bind GTP. As long as the G protein is bound to GTP, it is in the on position and activates additional proteins in the signaling pathway.
some g proteins are composed of three subunits: alpha, beta and gamma
the alpha subunit is the part of the G protein that binds to eitehr GDP or GTP
when GDP bound to the alpha subunit is replaced by GTP the alpha subunit seperates from the beta and gamma subunits
in most cases, the siolated GTP bound subunit becomes active and is able to bind to target proteins in the cell
G protein were disocvered by Gilman and Rodbell when studying adrenelaine
Neer pioneered stuides on the structrue of G proteisn adn theri role as moleuclar switches inside of the cells
Signals are often amplified in the cytosol
Adrenaline, discussed earlier, binds to a G protein-coupled receptor. When adrenaline binds to its receptor on cardiac muscle cells, GDP in the G protein is replaced by GTP and the G protein is activated.
The gtp bound alpha subunit then binds to and activates an enzyme in the cell memrbane called adenylyl cyclase
adenylyl cyclase converts the nucleotide ATP into cyclic AMP
cAMP is known as the second messenger
second messengers are isgnaling moelcules fond inside cells that relay info to the next target in the signal trasnudction pathway
ex. the second messenger cAMP binds to and actviates protein kinase A (PKA)
adrellnne and growth fatcors are considered first messengers
A little adrenaline goes a long way as a result of signal amplification (Fig. 9.12). First, a single receptor bound to adrenaline can activate several G protein molecules. Next, each molecule of adenylyl cyclase catalyzes the production of large amounts of the second messenger cAMP. Then each PKA molecule activates multiple protein targets by phosphorylation. These sequential molecular changes in the cytosol amplify the signal so that a very small amount of signaling molecule has a large effect on a responding cell.
