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Posted by on May 21, 2013 in Explain To Me |

Explain To Me: Receptor Upregulation/Downregulation

Explain To Me: Receptor Upregulation/Downregulation

Do you have any questions about up-/down-regulation? Head for the “Why Is It All So Confusing?” forum and we'll try and help.

Let's start with the ever-so-helpful Wikipedia definition of upregulation and downregulation:

Downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external variable. An increase of a cellular component is called upregulation.

Got that?

No?

Me neither …

Let's backtrack a bit and see the whole picture first:

Cell Signalling

In order to respond to changes in their immediate environment, cells must be able to receive and process signals that originate outside their borders. Individual cells often receive many signals simultaneously, and they then integrate the information they receive into a unified action plan.

What Is A Receptor?

A receptor is a protein, usually found on the surface of a cell, that receives chemical messengers from outside the cell. When such external substances bind to a receptor, they direct the cell to do something, such as divide, die, or allow specific substances to be manufactured, enter or exit the cell.

Watch the following 27 sec. video snippet and see how a ‘chemical messenger from outside the cell'  (in green) arrives near a cell and connects (binds) with the receptor (in brown) and how, as a consequence of the binding, the receptor transmits a signal, through the cell membrane, into the cell.

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In the instance in the snippet, you saw one “receptor” receiving a “chemical message”. In fact, there are hundreds of receptor types found in cells, and varying cell types have different populations of receptors.

Also, the “chemical message” in the snippet was a hormone, but there are many types of messages that can be received by cells : hormones (message from the endocrine system), neurotransmitters (message from the nervous system), cytokines (message from the immune system), growth factors or cell recognition molecules, toxins and others)

How Do Cells Recognize Signals?

A particular cell is a target cell for a chemical message if it contains functional receptors for that chemical message, and cells which do not have such a receptor cannot be influenced directly by that chemical message. Reception of a radio broadcast provides a good analogy. Everyone within range of a transmitter for National Public Radio is exposed to that signal. However, in order to be a National Public Radio target and thus influenced directly by their broadcasts, you have to have a receiver tuned to that frequency.

So, the ability for a cell to respond to a message depends on the presence and and the number of receptors tuned to that message. The more receptors on a cell tuned to the same message, the louder the cell hears the message and the more actively the cell responds to the message.

The Life-Cycle of Receptors

Receptors are born in the cell. The cell's DNA contains the instructions to create each type of receptor. The cell runs the DNA program, which results in the creation of a receptor protein, and that receptor protein is then pushed out to the cell boundary and embedded in the cell's membrane. This is called ‘expression'  of the receptor. Once receptors have been expressed, the cell can receive and respond to messages the receptor is tuned to.

But the receptors have a life cycle.

They can be taken out of the membrane and recycled into the cell. So fewer receptors are left on the cell membrane and therefore the less notice is being given to that specific  message. So a decrease in the number of receptors to a message sited on the cell membrane reduces the cell's sensitivity to the message.

That's called down-regulation.

Similarly if the cell receives a weak signal, it can up-regulate by pumping out more receptors such as to increase the sensitivity to the weak message. So an increase in the number of receptors to a message sited on the cell membrane increases the cell's sensitivity to the message.

That's called up-regulation.

So this is a very flexible and changeable environment; the cell is constantly monitoring what's coming in to its receptors and adjusting their quantities accordingly.

Now watch the following 87 sec. video snippet. It shows a neuron cell receiving an opiate “message”. Keep the video slider visible so that you can follow the timer against the description below:

  • at 1:30 – you can see the binding of the opiate to the receptor
  • at 1:46 – the receptor is ingested for recycling
  • at 1:59 to 2:16 – receptors are constantly being absorbed and recreated
  • at 2:47 – receptor downregulation
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Now re-read the Wikipedia entry at the beginning of the post and see whether you understand it.