Chapter 11: Cell Communication Flashcards
Quorum sensing
Process by which bacteria monitor their local cell density by sensing the concentration of signaling molecules secreted by other bacteria
Allows populations to coordinate the behavior of all cells in a population’s activities that require a given density of cells acting at the same time
E.g., formation of a biofilm- an aggregation of bacterial cells attached to a surface by molecules secreted by the cells after the cells have reached a certain density
Signal transduction pathway
Series of three major steps:
- Signal reception- detection of a signaling molecule when it binds to a receptor protein located on the cell’s surface
- Signal transduction- signaling molecule causes a confirmational change in the receptor protein which converts the signal to a form that can bring about a specific cellular response
- Cellular response- transduced signal triggers a specific response which could include any cellular activity
Communication by direct contact
Local Signaling
Paracrine signaling- Signaling molecules secreted by signaling cells travel only short distances and influence nearby cells
Synaptic signaling- occurs in the nervous system of animals
Ligand
A molecule that specifically binds to another molecule
Common membrane receptor proteins
Three main types of membrane receptors:
- G protein-coupled receptors (GPCRs)
- Receptor tyrosine kinases
- Ion channel receptors
G protein-coupled receptors
G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors
G proteins bind the energy-rich GTP
G proteins are all very similar in structure
Receptor tyrosine kinases
Receptor tyrosine kinases (RTKs) are membrane receptors that attach phosphates to tyrosines
A receptor tyrosine kinase can trigger multiple signal transduction pathways at once
Ion channel receptors
A ligand-gated ion channel receptor acts as a gate when the receptor changes shape
When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptor
Intracellular receptors
Intracellular receptor proteins are found in the cytoplasm or nucleus of target cells
Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors
Examples of hydrophobic messengers are the steroid and thyroid hormones of animals
An activated hormone-receptor complex can act as a transcription factor, turning on specific genes
Signal transduction
Signal transduction usually involves multiple steps
Two benefits to a multistep process:
- It can greatly amplify a signal
- Pprovide more opportunities for coordination and regulation of the cellular response
Protein phosphorylation and dephosphorylation
Widespread cellular mechanism for regulation
Protein kinases transfer phosphates from ATP to protein in a process called phosphorylation
- RTKs are a specific kind of protein kinase that phosphorylates tyrosines on the other RTK dimer
- Most cytoplasmic protein kinases phosphorylate either serine or threonine rather than tyrosine such as serine and threonine kinases
Many relay molecules create a phosphorylation cascade
Protein phosphatases rapidly remove the phosphates from proteins in a process called dephosphorylation which enable protein kinases to be reused
Second messengers
Small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion and participate in pathways initiated by GPCRs and RTKs
Cyclic AMP and calcium ions are common second messengers
Cyclic AMP
A small molecule produced from ATP by a plasma membrane called adenylyl cyclase in response to an extracellular signal
- In the case of epi, when it binds to a GPCR it activates a G protein that in turn activates adenylyl cyclase to catalyze the synthesis of many molecules of cAMP
- This boosts the cellular concentration of cAMP by as much as 20-fold in a matter of seconds which broadcasts the signal to the cytoplasm
The immediate effect of an elevation in cAMP level is usually the activation of a serine/threonine kinase called protein kinase A
cAMP does not persist for long and is broken down by the enzyme phosphodiesterase which converts cAMP back into AMP
Cholera pathophysiology
The cholera bacterium, Vibrio cholerae, produces a toxin that modifies a G protein so that it is stuck in its active form
This modified G protein continually makes cAMP
Causes intestinal cells to secrete large amounts of salt into the intestines
Water follows by osmosis and an untreated person can die from the loss of water and salt
Calcium ions as a second messenger
Even more common second messenger than cAMP
Functions in pathways triggered by both GPCRs and RTKs
Ca2+ can function as a second messenger because its concentration in the cytosol is normally much lower than its concentration outside the cell
Ca2+ are actively transported out of the cell and out of the cytosol into the ER (and sometimes the mitochondria) by various protein pumps
In response to a signal relayed by a signal transduction pathway the cytosolic Ca2+ level may rise, usually by a mechanism that releases Ca2+ from the ER
The pathways leading to calcium release involve two other secondary messengers, inositol triphosphate (IP3) & Diacylglycerol (DAG) which are produced by cleavage of a certain kind of phospholipid in the plasma membrane
Cellular response
The cell’s response to an extracellular signal is called the output response which leads to the regulation of cellular activities in the cytoplasm or the nucleus
Many signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus
The final activated molecule in the signaling pathway may function as a transcription factor
Regulation of the cellular response
A response to a signal may not be simply “on” or “off” but may be regulated in multiple ways
There are four aspects to consider:
- Amplification of the signal and thus the response
- Specificity of the response
- Overall efficiency of response, enhanced by scaffolding proteins
- Termination of the signal
Signal amplification
Enzyme cascades amplify the cells response to the signal
At each step the number of activated products is much greater than in the preceding step
Signal specificity
Multistep pathway provides control points at which the cell’s response can be further regulated and coordinated with other pathways
Different kinds of cells have different collections of proteins
The same signal can have different effects in cells with different proteins and pathways
- Epinephrine has different effects on the liver than the heart
Pathway branching and “cross-talk” further help the cell coordinate incoming signals
Signaling efficiency
Efficiency of the response is enhanced by the presence of scaffolding proteins- large relay proteins to which other relay proteins are attached
Increase the signal transduction efficiency by grouping together different proteins involved in the same pathway because the rate of protein-protein interaction is not limited by diffusion
May also help activate some of the relay proteins
Termination of the signal
Inactivation mechanisms are an essential aspect of cell signaling
If ligand concentration falls, fewer receptors will be bound
Unbound receptors revert to an inactive state
Apoptosis
Components of the cell are chopped up and packaged into vesicles that are digested by scavenger cells
Prevents enzymes from leaking out of a dying cell and damaging neighboring cells
The main proteases of apoptosis are called caspases
Apoptosis can be triggered by signals from outside the cell or inside it
Internal signals can result from irreparable DNA damage or excessive protein misfolding
