G protein coupled receptors

Discuss the mechanism(s) by which you think free calcium and calcium ion in the presence of calmodulin might influence adenylyl cyclase specific activity?

I know that calmodulin binds the calcium which is a secondary messenger and that adenylyl can be located near clacium channels for quicker reactions to ca2+ influx but im not sure of the effect it woud have directly?

Reply 1

Eloades11

17

Original post by mariek03

Discuss the mechanism(s) by which you think free calcium and calcium ion in the presence of calmodulin might influence adenylyl cyclase specific activity?

I know that calmodulin binds the calcium which is a secondary messenger and that adenylyl can be located near clacium channels for quicker reactions to ca2+ influx but im not sure of the effect it woud have directly?

It has been a while since I covered this, so I had to refresh my memory before replying. What you've stated is correct. The key factor to take in here is what the function of calmodulin is. Calmodulin can directly bind 4 calcium ions inside the cell, which in turn lowers the intracellular calcium levels. If calmodulin was present, this would bind calcium preventing any interaction with adenylyl cyclase. This would inhibit the conversion of ATP to cAMP I believe, I could be wrong.

Reply 2

mariek03

OP

thanks

would there still be some conversion as calcium is a secondary messenger would adenylyl not have a first messenger that would still work or am I think about this wrong :/

Reply 3

Eloades11

17

Original post by mariek03

thanks

would there still be some conversion as calcium is a secondary messenger would adenylyl not have a first messenger that would still work or am I think about this wrong :/

You'll have to forgive my first post since my main source was wikipedia, but it appears there's more information on this than wikipedia claims. "The presence of calmodulin appears largely responsible for the ability of the adenylate cyclase enzyme to be stimulated by submicromolar concentrations of calcium; it may not be relevant to the inhibition of the enzyme which occurs at higher concentrations of calcium.". This shows there is a direct relationship between calcium and adenylyl cyclase activity which, most of these papers describe as having an important relationship in neuronal cells. I strongly recommend looking through some of these papers as they are a very interesting read.

The paper listed below was published in 1985, and it states in the abstract "The physical relationship of calmodulin to the plasma membrane bound enzyme (or to the soluble forms of the enzyme) is not known nor is the mechanism of adenylate cyclase activation by calmodulin clear; current data suggest some involvement with both the N and C units of the enzyme.". It has probably been looked at since then and you should easily be able to find a more recent study looking at the interaction between calmodulin and andenylyl cyclase.

Quote me if you can't find it or still need help :smile:

Here are some sources:
Research article, Calmodulin regulation of adenylate cyclase activity.:
http://www.ncbi.nlm.nih.gov/pubmed/3893727
Review on calmodulin activated andenylyl cyclases: http://physiologyonline.physiology.org/content/19/5/271
Research paper, experimental evidence demonstrating calcium as a significant benefactor in adenylyl cyclase activity for memory in mice: http://www.ncbi.nlm.nih.gov/pubmed/10482244

Reply 4

SmashConcept

20

Original post by mariek03

Discuss the mechanism(s) by which you think free calcium and calcium ion in the presence of calmodulin might influence adenylyl cyclase specific activity?

I know that calmodulin binds the calcium which is a secondary messenger and that adenylyl can be located near clacium channels for quicker reactions to ca2+ influx but im not sure of the effect it woud have directly?

I'm not sure I understand the distinction you seem to be making between a "direct" effect and an indirect one.

Reply 5

SmashConcept

20

Actually sorry, I do understand the distinction you're making. This is just Wiki stuff, and like @Eloades11 I'm rusty on any of this (if I even had a good understanding of it before). This part from the adenylyl cyclase might be instructive, at least in terms of where the confusion is coming from.

Regulation[edit]

Adenylyl cyclase is dually regulated by G proteins (Gs stimulating activity and Gi inhibiting it), and by forskolin, as well as other isoform-specific effectors:

•

Isoforms III, V and VIII are also stimulated by Ca ²⁺/calmodulin.

•

Isoforms I and VI are inhibited by Ca²⁺ in a calmodulin-independent manner.

•

Isoforms II, IV and IX are stimulated by beta gamma subunits of the G protein.

•

Isoforms I, V and VI are most clearly inhibited by Gi, while other isoforms show less dual regulation by the inhibitory G protein.

Since there's calmodulin dependent and independent regulation, upregulated presence of calmodulin might affect isoforms I and VI indirectly by binding with their inhibitor (although you would need more evidence that this actually happens than my speculation to write it in your essay). Isoforms III, V and VIII are presumably the ones discussed in the first link Eloades11 posted, and their activities are upregulated by calcium bound calmodulin. According to this link - and again, we all know it isn't the word of God - calcium does not have any mechanism for calmodulin independent upregulation of AC, which is what you seemed to be asking about.

Hope this helps, I understand that I don't communicate very well on subjects like this so let me know if there is anything you need me to clarify.

G protein coupled receptors

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