« How to see a black hole birth | Main | Bursting the bubble around "water worlds" Kepler-62e and -62f »
Wednesday
May012013

Learning: What’s programmed cell-death proteins got to do with it?

by Brooke Napier

A. Healthy Cell :) B. Apoptotic Cell :(Apoptosis is programmed cell death. It is controlled cellular suicide that is responsible for humans not having webbed fingers.  Less dramatically this time - apoptosis effectively and efficiently removes extra and unnecessary cells during development.

Cellular proteins called caspases control apoptosis. Caspases are a family of proteins known as cysteine proteases and they mediate cell suicide by forming protein complexes with activating complexes in the presence of adaptor proteins. They cleave other caspases and other cellular substrates to orchestrate a very controlled cellular destruction.

Humans encode 11 caspases, and while most of them dedicate their folded-life to carrying out apoptosis, some caspases have been known to dabble in immune regulation (ex: containing inflammation during infection to the site of infection) and spermatogenesis (you’ll have to ask a sperm-centric Ph.D. candidate about this one).

Mouse interdigits in utero - red cells are apoptotic. Fingers, ya'll!Although I have previously emphasized the importance of apoptosis/caspases in the development of our digits (I <3 my thumbs), ANTI-apoptotic molecules (members of the BCL-2 family) are extremely important during the development of the brain. There is relatively little turnover in the brain, so maintenance of differentiated neurons (peripheral neurons specifically) is very important.

Since apoptosis is specifically down-regulated in many neurons, one would assume that after development of the human brain caspase proteins are no longer needed in a healthy human. But then why have so many researchers found that caspases are required normal, everyday neural functions?

Caspases are serving a completely different function in the healthy adult human brain.

Ah ha! It turns out caspases can also dabble in other, very important neuronal functions. In fact there is data showing that activation of caspases in neurons can control normal neural physiology.

What are the new roles for caspases in neural physiology?

Ye ole dendrite. Gorgeous as ever.

1) Dendritic pruning, or trimming the hedges, if you will. Dendrites (from the word tree in Greek) are beautifully branched neurons that transmit electrochemical stimulation from other neural cells to the soma, or cell body, of the dendrite, which then makes the executive decision to pass on the electrochemical signals to more dendrites via neurochemical synapses. This is the beautiful orchestra that is neuron-to-neuron communication in the nervous system.

Pruning of the dendrites is important for normal brain functions, it removes neglected or misguided dendritic branches, which would normally get in the way of forming fresh, new, sparkly synapses. Just like learning, the formation of our neural connections are fluid, and caspases grease the spokes.  This mechanism of plasticity is as important as it sounds; Caspase 3 has been implicated in the zebra finch and fly models of learning and memory.

2) Axon guidance and synaptogenesis. Basically if you make a mouse that is caspase-deficient you have successfully made a mouse that has defects in axon targeting and synapase formation during development, which leads to significant developmental delays.

After poking my nose into this research, it seems like not a lot is understood about how caspases effect axon guidance or synapse generation – but there is preliminary data that suggests without some specific caspases axons show delayed/misguided maturation and some proteins required for synapse generation are impaired.

3) Normal synaptic physiology, turns out low levels of caspase 3 activation are required for synaptic changes that underlie memory.

Related, long-term depression (LTD), where synapses become less sensitive to stimulus (and the dendritic branches shrink or get eliminated), is associated with local activation of Caspase 3. Turns out, if you block caspase 3 or 9 activation you can effectively stop LTD! Follow the Figure legend below to learn more about this mechanism.

Too bad we can prescribe caspase 3 inhibitors for patients diagnosed with LTD (remember all the other things caspases do?).

The once infamous rapid-cell-death associated family of proteins has now relinquished its former title and should now be referred to as: Caspases: the we-can-help-you-learn family of proteins. In the words of Bradley Hyman and Junying Yuan:

“In addition to being a signal of acute, inexorable death, caspase activation in other circumstances (at least within the CNS) might instead be a pivotal event for responding to ever-changing environmental stimuli.”


ResearchBlogging.org Hyman, B., & Yuan, J. (2012). Apoptotic and non-apoptotic roles of caspases in neuronal physiology and pathophysiology Nature Reviews Neuroscience, 13 (6), 395-406 DOI: 10.1038/nrn3228

EmailEmail Article to Friend

References (109)

References allow you to track sources for this article, as well as articles that were written in response to this article.
  • Response
    Response: fix pc error
  • Response
  • Response
    Response: lead generation
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: auckland roofing
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: Magician NJ
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: Hay Day Hack
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: whiteboard paint
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: agencia seo
    click here for best blog seo around
  • Response
    Response: make money online
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: computer glasses
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: www.reddit.com
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: HRV
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: rbse result 2014
  • Response
    Response: Hay Day Cheats
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: 301 nuke review
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: dental implants
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: online auctions,
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: GU10 led bulbs
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: www.niagara.com.au
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: Construction leads
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: Contractor leads
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: Neundenker
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: C and D Towing
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: london escorts
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: Events Security
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: Parquet Flooring
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: dosismusical.com
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: Hand Tools Europe
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: buy goji vita
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: ugg outlet
    For instance ,ugg boots outlet online, A2z tony Iommi, Jimi Hendrix,fitflo ugg boots outlet online ps, Henry McCartney,ugg o fitflops utlet, together with Kurt Cobain to mention a few. The particular playing golf ecommerce site often is the most effective provider for choosing most o ugg outlet f
  • Response
    Response: mma muscle pro
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: team National
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: kd 6
    Solution can be 12.0Megapixel(interpolation). Cli buy celine handbags entele who wishes to come w balenciaga bag ith an on location stop by to it's office are extremely substantially pleasant. You will be want to hold out that long and provide to rush upward intended for alternat pandora charms ive job
  • Response
    The reality is, with the outlook during increasing kids ph chloe handbags ysical and mental point out,chloe handbags, using ball delivers the comparabl nike roshe run women e purpose by way of playing keyboard. Sprinkle from that containers and even live in harmony during infestations 1 woolrich outlet store 0
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: gucci handbags
    Consequently, look out and about with regard to real, and also sugary tryin nike high heels g smoke a pipe. Ones o red wing shoes wn company for investigators are constantly finding ways to earn rubbers that much more attractive not to mention fulfilling for his or her consumers,ni babyliss pro ...
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: Rogers plumbers
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: Review
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: Review
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: http://www.zioh.de
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: Visalus
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: cheap escorts
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: Vigrx oil
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: cheap escorts
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: london escorts
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
    Response: go to these guys
    Learning: What’s programmed cell-death proteins got to do with it? - Blog - Smaller Questions
  • Response
  • Response
  • Response
    Response: Happy Mothers Day
  • Response
  • Response
    Response: Today's Business
  • Response
    Response: Cartoon Images
  • Response
  • Response
    Merry Christmas
  • Response
    Merry Christmas 2015
  • Response
  • Response
  • Response
    Response: العاب
    العاب
  • Response
    Response: TheBostonProject
    very interesting subject , appreciate it for putting up.
  • Response
    Grand National 2016
  • Response
  • Response
    Response: mobdro
  • Response
  • Response
  • Response
    Response: French Open 2016
    Roland Garros 2016
  • Response
    Response: Easy ecom
  • Response
  • Response
  • Response
    Response: Super Bowl
  • Response
    Response: Gmail Sign In
  • Response
    Response: xmeye for PC
    download xmeye
  • Response
  • Response
    Response: ahad dfb
  • Response
    Response: UFC 213 live1
  • Response
  • Response
    Response: live
  • Response
    asdasdaf
  • Response
    Response: shareit
  • Response
    ACER
  • Response
    Response: Yahoo Tech Support
    Raghuvandra
  • Response
    dr puma

Reader Comments (7)

There are many types of protein and many debates on which is best to use as a muscle gainer. Experience tells me that there is no major difference between Concentrate, Isolate or Casein protein powders and I have tried all types in different stages of my training.

April 22, 2014 | Unregistered CommenterProtein Tozu

Great Article
ipl schedule

January 29, 2015 | Unregistered Commenteripl schedule 2015

Happy Easter
Great Post

January 30, 2015 | Unregistered CommenterEaster Wishes 2015
February 3, 2015 | Unregistered CommenterIRCTC Login Page

I have made a huge collection of Happy Easter Day Images and pictures...Go and get them for free.
Happy Easter Day 2015
Happy Easter Images 2015
Funny Easter Images

March 28, 2015 | Unregistered CommenterSanju

Hello man. I really liked your blog and want to confess that you are awesome also i have made a blog on Muttertag 2015 and please give me feedback for this blog so that i can improve from your valuable comment.

April 21, 2015 | Unregistered CommenterYatin

hi dear keep going in this way you provide lot of useful information.

March 14, 2017 | Unregistered Commentermobdro for android

PostPost a New Comment

Enter your information below to add a new comment.

My response is on my own website »
Author Email (optional):
Author URL (optional):
Post:
 
Some HTML allowed: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <code> <em> <i> <strike> <strong>