The enzymes nitric oxide (NO) synthase (NOS1) and protein kinase C (PKC) play an important role in a variety of signal transfer processes in neurons of the brain, as well as in many cell types of other organs. the The scientists have shown for the first time that enzymes can be activated under physiological conditions through sole electrical stimulation of the cell membrane. Protein super complexes that rapidly transform electrical signals at the cell membrane into chemical signal processes inside the cell emerge through direct structural interaction of both enzymes with voltage-gated calcium channels. The researchers have presented their work in the journal Proceedings of the National Academy of Sciences (PNAS).
The group has previously shown that both calcium-dependent enzymes NOS1 and PKC are components of the protein nano-environment of certain voltage-gated calcium channels (Cav2-channels) in the brain. As yet, however, it was not know how these enzymes communicate with the calcium channels. The research group has now found that both enzymes are integrated into protein super complex with Cav2 channels.
Within such Cav2-NOS1/PKC complexes NOS1 or PKC are anchored at the cytoplasmic side of the cell membrane and are placed at in the immediate vicinity of the channel pore. Upon excitation of the cell membrane, the Cav2 channels open and deliver calcium ions to the cell cytoplasm, where they bind to both enzymes. Calcium binding activates the enzymes, which subsequently produce the diffusible second messengers NO or phosphorylate cytoplasmic target proteins.
Due to the proximity between channel and enzyme, electrical stimulations of less than a millisecond duration are required for effective electro-chemical coupling. The latter becomes maximal when the cell, instead of being stimulated by individual impulses, fires action potentials with a frequency of one hertz or more.
The Cav2-enzyme super complexes not only guarantee an ultrafast and reliable electro-chemical coupling. They also ensure that signal transduction remains locally restricted, that is, within an area less than a few nanometers around the Cav2 channels. This local restriction guarantees that the enzymes only initiate specific cellular processes, while other calcium signalling pathways, including cell death, are prevented. In addition, the researchers' experiments highlighted the physiological mechanism for activation of NOS1 and PKC thus presenting an alternative to the widely used synthetic activators, such as NO donors or diacylglycerols.
https://www.pr.uni-freiburg.de/pm-en/2017/how-enzymes-communicate?set_language=en
http://www.pnas.org/content/early/2017/05/10/1616394114
Latest News
A drug to prevent flu-induc…
By newseditor
Posted 18 Apr
New origin of deep brain waves
By newseditor
Posted 17 Apr
Starving cells hijack prote…
By newseditor
Posted 17 Apr
Miniature battery-free epid…
By newseditor
Posted 17 Apr
Molecular causes of differe…
By newseditor
Posted 16 Apr
Other Top Stories
A wireless closed-loop system for optogenetic peripheral neuromodul…
Read more
Detecting Alzheimer's disease six months before diagnosis using AI
Read more
Inhalable form of messenger RNA created!
Read more
Safer and more efficient gene editing!
Read more
LEDs to improve health, food!
Read more
Protocols
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Modular dual-color BiAD sen…
By newseditor
Posted 31 Mar
Publications
How does the microbiota con…
By newseditor
Posted 18 Apr
The integrated stress respo…
By newseditor
Posted 18 Apr
The immunobiology of herpes…
By newseditor
Posted 17 Apr
Circulating microbiome DNA…
By newseditor
Posted 17 Apr
Spindle oscillations in com…
By newseditor
Posted 17 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar