BIS 2D Module 4 Cell Communication

Cell signaling

Mechanisms in place in cells that allow them to respond to signals inducing a response or change of behavior

What are the steps for cell signaling?

1. Monitoring

2. Processing

3. Responding

Monitoring in cell signaling

Process by which a cell monitors their environment for signals through receptors

Processing in cell signaling

Information collected by receptors are processed by intracellular signaling molecules

Responding in cell signaling

Information is processed by effector proteins that change the cell behavior: metabolic protein, transcription factors, cytoskeleton protein, etc.

Describe an extracellular signal

can be proteins, amino acids, nucleotides, steroids, fatty acids, gases, and light; depending on their nature their receptor may be on the surface of the cell (the plasma membrane) or be intracellular

What are the different types of extracellular signals?

endocrine, paracrine, neuronal and cell to cell communication

Rank the extracellular signals by speed from least to greatest

Endocrine < Paracrine < Cell-to-cell communication < Neuronal

Rank the extracellular signals by range from least to greatest

Cell-to-cell communication < Paracrine < Neuronal < Endocrine

What are hormones?

proteins that regulate paracrine and endocrine extracellular signaling

What is a receptor?

a protein that can switch between OFF and ON (and indeed back to off) (typically by a conformational change) and transmit the information so there is a change in cell behavior

What are the 4 types of receptors?

ion channels coupled receptors, G protein-coupled receptors, enzyme coupled receptors and intracellular receptors

What are enzyme-coupled receptors?

Single pass transmembrane proteins that are enzymes themselves; they are associated with another protein in the cytosolic side that is the enzyme

What do enzyme-coupled receptors do in the presence of a ligand?

two receptors dimerize making possible the activation and recruitment of different intracellular signaling molecules

What are enzyme-coupled receptors used for?

They can be involved in rapid response but they are mainly related with changes in gene expression

What enzymatic activity do enzyme-couple receptors have?

kinase

Describe the cascade response of enzyme-coupled receptors

There are two receptors and the ligand binds the two together causing a conformational change to activate the receptor; once the change occurs the receptor will phosphorylate other proteins and themselves which changes the activity of other proteins

What is the largest family of cell surface receptors?

G-protein coupled receptors (GPCRs)

What is a G-protein coupled receptor (GPCR)?

Seven passes transmembrane proteins coupled with G-proteins (composed of three subunits alpha, beta, and gamma)

What happens when a GPCR is activated?

ion channels can be regulated and/or proteins that produce small intracellular molecules can be activated

What are GPCRs involved in?

in slow responses but they are mainly related with very fast changes in the cell

Describe the GPCR signal cascade

When the signal is received by GPCR, the G proteins subunits are separated by the conformational change and participate in their own signal cascade pathway

Why is there a difference in speed for receptor response?

We may need to wait for other cellular processes to occur so the receptor response can be completed

What do signal cascades do?

1. Relay signals downstream

2. Amplify signal with the use of small intracellular molecules

3. Integration of more than one intracellular pathway

4. Distribute the signal to more than one effector protein

5. Feedback: Modify the activity of elements upstream of the pathway

Describe the role of amplification in signal cascade?

When the receptor is activated, the protein it is associated with may make a secondary messenger to amplify the signal to ensure there is a quick and accurate response

What are the conditions for the ions to move across a channel once it is open?

There must be a concentration gradient

Why does potassium accumulate in cells?

Because many of the molecules we have such as DNA are negatively charged and through evolution, potassium is used to mediate the negative charge

What creates the concentration gradient for ion transport across channels?

The high concentration of potassium inside the cell and high concentration of calcium outside the cell

What is an electrochemical gradient?

The idea that a gradient is formed due to a difference in concentration between the potassium in a cell and calcium outside the cell

Describe how homeostasis and ion concentration are related?

Maintaining the proper concentration of K in the cell and Na outside the cell is important for maintaining homeostasis in the cell in terms of water movement and ion concentration

Why do we have a K non-gated channel in cells?

non-gated = always open; K would flow out of the cell to help maintain homeostasis

Why do we have Na non-gated channel?

Allows Na to flow into the cell to maintain homeostasis

What is the standard potential for a all animal cells at resting conditions why?

Due to non-gated Na and K channels that allow K to flow out of the cell and Na to flow into the cell, the membrane potential is about -70 mV to control osmotic pressure

What are sodium/potassium ATPases?

a type of active transporter that consumes ATP to transport Na/K against the concentration gradient to compensate for the unbalance electrochemical gradient in animal cells

Why do we call the potential "-70"?

Because the interior of the cell is negatively charged and positively charged outside the cell

How much ATP is used by Na/K ATPases?

1/3 of the ATP produced by the cell

Distinguish dendrite, axon hillock and axon terminal in the neuron morphology

1. Dendrites are the small appendages coming from the cell body

2. Axon hillock is the area of the axon at the transition from the cell body to the axon

3. Axon terminals are the appendages coming from the end of the axon

How can measure membrane potential of a neuron?

We measure inside and outside the axon and measure the voltage in both spaces to determine the potential

What is the action potential?

+40 mV

How does the cell move from -70 mV to +40 mV?

Conformational change in an the TRPC ion channel can allow the entrance of Ca to increase the membrane potential

What cells are excitable/have the ability to change their action potential when there is a change in voltage?

Neurons and muscle cells

What distinguishes excitable cells from other cells?

They have channels in their plasma membrane that can opened in response to stimulus called gated channels

What are the 4 types of gated channels?

1. Voltage-gated

2. Chemically-gated

3. Mechanically-gated

4. Thermally-gated

Voltage gated channel

If the membrane potential changes then there is a conformational change that opens the channel

Chemically gated channel

When they bind to ligands, it causes to the channel to open which allows ions to move through

Mechanically gated channel

Channels that respond to some sort of mechanical change (pressure)

Thermally gated channel

Channels that respond to some sort of change in temperature

Describe the steps for action potential/depolarization?

1. TRPC opens in response to high T and Ca enters the cytosol changing membrane potential

2. Change in membrane potential opens a voltage-gated channel that allows Na to flow into the cell.

3. The change in membrane potential propagates

Describe the steps for repolarization

1. Potassium leaves through the potassium-voltage gated channel

2. Na channel closes

3. Na/K ATPase restores the Na/K as it was in resting conditions

Why do we go back to resting potential?

1. To maintain homeostasis/osmotic pressure

2. So we are ready for another change in membrane potential

What is the synapse?

The space between the two neurons

Pre-synaptic neuron

The neuron that has the action membrane potential fire (heat)

Post-synaptic neuron

The neuron after the pre-synaptic neuron that needs to receive information

In a neuron what happens after the Ca voltage-gated channel is open in the pre-synaptic neuron?

The calcium accumulates where there are vesicles full of neurotransmitters. The vesicles will then fuse with the plasma membrane where the neurotransmitters are released in the synapse

In a neuron what happens after the neurotransmitters are released in the synapse?

The neurotransmitter goes to the post-synaptic neuron where it binds to a ligand-gated channel in the axon terminal

What is the significance of the axon hillock?

Collects all the information that is transmitted from other neurons; it is very enriched in Na voltage-gated channels; this region is in charge of firing the action potential if the summation of the changes on membrane potential induced in the body and dendrites of the neuron reach the threshold

Excitatory synapses

neurotransmitter opens ligand-gated channels that can be used by Na and K; allowing us to reach an action potential by increasing the membrane potential (allows more Na than K)

Inhibitory synapses

neurotransmitter opens ligand-gated channels that allow the movement of Cl or ligand-gated channels that allow the movement of K; makes it more difficult to reach an action potential by decreasing the membrane potential