Navigation Links
Breakthrough technology observes synapse in real time, supporting theory of vesicular recycling
Date:12/14/2007

NEW YORK (Dec. 13, 2007) -- For the first time, scientists at Weill Cornell Medical College in New York City have observed in real time a cellular mechanism that's crucial to how brain cells communicate.

In doing so, they've also laid to rest a competing theory as to how key cellular processes -- called endocytosis and exocytosis -- work.

The scientists published their findings in this week's online edition of Proceedings of the National Academy of Sciences (Dec. 18 print edition).

Healthy neurological function hinges on the efficient passage of information between brain cells via the synapse, and exocytosis/endocytosis is the complex trafficking mechanism that allows this to happen.

At its simplest level, exocytosis involves the packaging, transport and delivery of neurotransmitter chemicals in sac-like structures called vesicles. These vesicles move from the interior of the cell to the cell membrane, where they deliver their information-rich cargo to the synapse. Endocytosis involves a similar function in the reverse direction, with incoming vesicles being transported into the cell's interior.

The vesicles aren't discarded, however. Instead, once they release their cargo they are recycled for use in another go-round. There have been two competing theories about how that recycling occurs -- either the vesicle fragments upon delivering its cargo and must be rebuilt, or it simply empties itself like milk from a bottle which is then resealed.

"The vast bulk of the evidence suggests the former theory is actually the correct one, but it's been tempting to think of the 'resealable spout' theory, because it seems so logical and because there's been some ambiguous evidence that it might be true," says the study's co-author Dr. Timothy Ryan, professor of biochemistry at Weill Cornell Medical College.

The trouble is, no one had ever found a way to observe -- accurately and in real time -- synaptic vesicle recycling as it occurs.

That has changed with this new paper. "We have taken advantage of recent advances in fluorescent 'tagging' of molecules involved in these cellular processes, as well as new microscopy technologies that give us an incredible new ability to watch all of this, up close and in real-time," says Dr. Ryan.

Specifically, Dr. Ryan used a fluorescent chemical stain called pHluorin and genetically fused it to a vesicular protein called vGlut1. "We've used this fluorescent tagging approach before, but with molecules that can exist on either the outside or the inside of the vesicle," Dr. Ryan notes.

"VGlut1 gives us a much more precise view, since it only inhabits the inside of the vesicle," he adds. "That means that when we see the green fluorescent tag move outside of the vesicle, then the vesicle itself must have ruptured in some way. This gives us a much more accurate picture of the recycling process."

At the same time, the team took advantage of new breakthroughs in optical microscopy that maximize how much of the tag's fluorescent light can be "grabbed" by the microscope. This approach allowed them, for the first time, to follow how individual synaptic molecules are delivered and retrieved from the synaptic surface.

"The result is an accurate view into this hitherto mysterious synaptic phenomenon," Dr. Ryan says.

The "resealable spout" hypothesis of vesicular recycling (also known as the "kiss-and-run" theory) may be the first casualty of this new insight.

"We observed that, although recycling appears to occur within a set but somewhat variable time-frame, it's still using the same mechanism -- the vesicle falls apart upon delivering its cargo to the cell membrane, and then enzymes go to work re-building it for the next cycle," Dr. Ryan adds. "I think this real-time observation really closes the door on the 'kiss-and-run' theory of vesicular recycling."

The new technology used in these experiments should bring scientists much more insight into how the synapse works generally, and that could have real implications for our understanding of neurological health and illness, Dr. Ryan says.

"This is all part of the 'shop manual' of neurological function that we are currently putting together, piece by piece," he says. "Discoveries like these are adding new pages to the manual every day, and it's that kind of knowledge that will someday save, extend and improve lives."


'/>"/>

Contact: Andrew Klein
ank2017@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Source:Eurekalert

Related biology news :

1. New technique can be breakthrough for early cancer diagnosis
2. Breakthrough research identifies how cells from pigs may cure diabetes
3. Male contraception breakthroughs to be presented, Seattle Sept. 27-28
4. Major genetic breakthrough for ankylosing spondylitis brings treatment hope
5. Oosight microscope enables embryonic stem cell breakthrough
6. Brain-computer link systems on the brink of breakthrough, study finds
7. Yale scientists use nanotechnology to fight E. coli
8. Voice Biometrics Gains Traction as Most Accurate and Convenient Technology to Secure Customer Privacy
9. M2SYS Partners with SecuGen Corporation to Support Market Leading Hamster Plus Fingerprint Reader with Auto-On Technology
10. Silicon Valley Technology Leaders LaserCard Corporation and Tesla Motors Sign LaserPass Secure Access Deal
11. Nanotechnology: Whats that?
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/30/2017)... ANGELES , March 30, 2017  On April ... Hack the Genome hackathon at Microsoft,s ... exciting two-day competition will focus on developing health and ... Hack the Genome is the ... been tremendous. The world,s largest companies in the genomics, ...
(Date:3/29/2017)... -- higi, the health IT company that operates the largest ... , today announced a Series B investment from BlueCross ... new investment and acquisition accelerates higi,s strategy to create ... health activities through the collection and workflow integration of ... and secures data today on behalf of over 36 ...
(Date:3/24/2017)... March 24, 2017 The Controller General of Immigration ... Abdulla Algeen have received the prestigious international IAIR Award for ... Continue Reading ... ... Deputy Controller Abdulla Algeen (small picture on the right) have received the ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... ... October 11, 2017 , ... The CRISPR-Cas9 ... overexpression experiments and avoiding the use of exogenous expression plasmids. The simplicity of ... performing systematic gain-of-function studies. , This complement to loss-of-function studies, such as ...
(Date:10/11/2017)... LAGUNA HILLS, Calif. , Oct. 11, 2017 ... London (ICR) and University of ... prognostic tool to risk-stratify patients with multiple myeloma (MM), in ... nine . The University of Leeds ... by Myeloma UK, and ICR will perform the testing services ...
(Date:10/10/2017)... (PRWEB) , ... October 10, ... ... development-stage cancer-focused pharmaceutical company advancing targeted antibody-drug conjugate (ADC) therapeutics, today confirmed ... targeted HPLN (Hybrid Polymerized Liposomal Nanoparticle), a technology developed in collaboration with ...
(Date:10/10/2017)... ... October 10, 2017 , ... ... optimization firm for the life sciences and healthcare industries, announces a presentation by ... Francisco. , The presentation, “Automating GxP Validation for Agile Cloud Platforms,” will present ...
Breaking Biology Technology: