9 - Signaling Pathways Directing Cell-Polarization I Flashcards
What is cell signaling necessary for?
Communications of the cell within itself or among cells in different tissues
What must cells take in information about?
Their environment, and their internal state
What decisions do cells have to make?
- What genes should be turned on/off?
2. What proteins should be activated/deactivated?
What are some responses cells could have through cell signaling?
Grow, divide, develop (migrate, change shape, etc.), survive, or die
What is cell signaling?
A language that cells use to communicate with one another and within themselves
True or false: the response of a cell is very specific
True: the nature of the signal and the integration of different signals makes the response highly specific
True or false: a signaling unit refers to a collection of proteins in a network
False: there are many different scales of signaling units (cell, protein, amino acid, etc.)
What is meant by the “universal nature” of signaling determinants?
While the context of the class will focus on neuronal development, these signaling determinants are found across different cells and different organisms as well
What is a state machine?
A machine that can acquire different states
What are some biological examples of state machines?
The whole cell, signaling determinants, etc.
What is a mechanical example of a state machine?
An automatic door
How does a state machine work?
An input changes the state of the machine, which leads to a different, specific function
When does a state machine change its state?
When it responds to a stimuli
True or false: a state machine can only be in two states
False: it can be in many different states depending on the state machine
Why can the cell be considered a state machine?
They take in inputs, change their state, and perform a specific function based on that state
What are some example states a cell could have?
Proliferating (growing), quiescent (surviving), and apoptotic (dying)
What are the different states controlled by?
Environmental inputs
True or false: a state machine can only have one input
False: it can integrate a combination of inputs
What is an example of states a protein can be in?
Phosphorylated or non-phosphorylated, ligand bound or non-ligand bound
What determines whether a kinase is active or inactive?
Its phosphorylation state
What determines whether a receptor is active or inactive?
Whether it is bound to a ligand
What is meant by a “hierarchal organization” of signaling devices?
Many components are signaling devices (organism -> cell -> kinase)
True or false: an amino acid in a protein can be a signaling device
True: there can be many scales of signaling devices
What is meant by an “upstream downstream hierarchy”?
Can have signaling events in order from beginning (upstream) to end (downstream)
What is usually the most upstream event in a signaling cascade?
Ligand binding to a receptor
What is meant by a signaling network?
Multiple proteins and pathways interact to yield a large signaling network
Which response would be hardest for a cell to achieve?
A prolonged response
Why would a prolonged response be hardest for a cell to achieve?
There are many feedback mechanisms that usually go to stop a signal
Why are multiple transient signals easier for the cell to achieve?
The cell engages in multiple pathways in a highly regulated manner
What is the most typical response of a cell?
An on/off response
True or false: if a response is difficult to achieve, a cell will not do it
False: while difficult, the cell can accomplish this
How does a cell measure its input?
Through its nature, strength, and changes over time
How long does neuronal development take?
Days
What is the significance of the time it takes for neurons to develop?
Takes a long time for cells to establish a sustained response
What is interesting about multiple inputs?
How they are regulated and controlled
True or false: cells are constantly bombarded with information
True: there is a lot of information the cell is receiving at a given time
What is meant by the nature of an input?
Is the input a growth factor, hormone, etc.
What is meant by the strength of an input?
The concentration gradient of the signaling molecule
True or false: it is possible for a cell to see zero concentration of a signaling molecule
False: there is always some present, which can be detected by the cell
What is meant by how an input changes over time?
Whether the input is constant, or the frequency of the input
What is the specific function of a cell determined by?
The nature and strength of the input, and the signaling determinants that it has
How can the signaling determinants of a cell determine the function?
These signaling determinants can drive a specific function based on the stimuli in that particular cell
How do proteins react to stimuli?
Allosteric switches, modular allosteric switches, or subcellular localization
What is an allosteric switch?
The protein receives an active state in response to a stimuli
What are some examples of allosteric switches?
Phosphorylation, ligand binding, etc.
What is a modular allosteric switch?
Domains of a protein can auto-inhibit the catalytic domain of the same protein
What are some examples of modular allosteric switches?
SH2 domains binding to catalytic subunits
What is an example of a protein-complex allosteric switch?
PKA
What is meant by subcellular localization?
Can change protein activity by changing its location in the cell
What is an example of subcellular localization?
A protein involved in gene expression is active when moved into the nucleus
True or false: cells respond to uniform concentrations of signals
False: they respond to gradients of signals
What is meant by conserved signaling mechanisms?
Cell signaling mechanisms can be seen in many different areas
What is an example of a conserved signaling mechanism?
Cell polarization
True or false: the world around us is symmetrical
False: it is asymmetrical and polar
True or false: a cell is a uniform unit
False: it is unique compartmentalized
What is the significance of a cell being uniquely compartmentalized?
The cell’s unique compartments can perform unique functions
What is cell polarization?
The ability to create/maintain morphologically/biochemically distinct domains (with unique sets of proteins) for distinct biological functions
What is the importance of asymmetric organization of the cell?
Be able to perform complex activites
What are examples of complex activities that require an asymmetric cell?
Cell-cell interactions, direction transport/secretion, cellular immunity, and development/morphogenesis
True or false: only the cytoplasm of the cell is compartmentalized
False: the plasma membrane can also be organized asymmetrically
How is a polarized phenotype achieved?
Through a complex interplay between gene expression, signal transduction, organelle biogenesis, cytoskeletal rearrangements, and membrane protein/lipid trafficking
How is polarity achieved on a molecular level?
Use stimuli to put certain molecules in specific places (pizza in the corner of a room)
What is the molecular distribution in a symmetric system?
Random distribution
How do molecules move from a symmetric to an asymmetric distribution?
By receiving particular inputs in a specific location (pizza in the corner of a room)
What is the basis of using specific stimuli to break symmetry?
Preferences for different stimuli
What is functional polarization?
Molecules grouped together can perform different functions based on different stimuli
What studies can be done in humans?
Diagnostics (imaging, limited histological/biochemical analysis)
What studies cannot be done in humans?
Studies that involve manipulation genetically, biochemically, or pharmacologically
What needs to be done to study cell polarization if humans cannot be used?
Need to use models
