NOV 26, 2016 3:19 PM PST

Cytoplasmic Droplet Formation is Related to Protein Regulation

WRITTEN BY: Carmen Leitch
First detected by Santiago Ramón y Cajal, there are strange droplets in the cytoplasm of cells that are not well understood. They are clumps of proteins that are amorphous, with no apparent structure and no membrane. There has been considerable interest in them lately, as they seem to be important to the activities and functions of the cell. They have also been linked to several diseases.
 
CPEB4 liquid-like droplets in the cell cytoplasm / Credit: J. Guillén-Boixet, IRB Barcelona
 
New work published in the journal eLife and led by Raúl Méndez and Xavier Salvatella, both researchers at the Institute for Research in Biomedicine in Barcelona (IRB), describes one example of the regulation and dynamics of these interesting protein aggregates. They have outlined how the protein clumps in this case make up an RNA binding protein called CPEB4.
 
CPEB4 is one of a family of proteins that are involved in many cell functions and have been associated with neurodegenerative diseases and cancer. CPEB4 seems to also function to activate or repress whether messenger RNA (mRNA) is translated into a protein by the cell – cells use messenger RNA as tool to copy genes from the genome so the cell can use its machinery to translate that copy into a protein. CPEB4 contains some sections that lack structure, remaining unfolded and flexible so that droplets can be both created and regulated during the cell cycle.
 
Previous work by these investigators demonstrated that CPEB4 controls the timeline of how cell division regulators are expressed. Jordina Guillén-Boixet, a postdoctoral fellow in Méndez's lab who is soon to continue work on these droplets in a lab at Max Planck in Germany, has spent seven years on the mechanics of CPEB4.
 
Guillén-Boixet found that CPEB4 proteins use their freeform parts to recognize one another, binding together to make the droplets. That sequesters mRNAs, keeping them from ribosomes, thus preventing protein translation. The characteristics of this aggregation allows for easy reversal when it’s the right time to translate RNA into proteins.
 

 
The research team has now determined exactly how the CPEB4 droplets form and break up during the cell cycle. They’ve also found the enzymes that phosphorylate various proteins needed to break down the aggregates and release the mRNAs. In the video above fro the new publication, live-imaging of a cell transfected with a GFP-tagged CPEB4 construct shows two liquid-like droplets fusing.
 
The researchers think that this research strengthens the veracity of two lines of thinking associated with the droplets. One is that the most RNA-binding proteins likely form these droplet organelles.
 
"[These organelles] were previously thought to be dispersed in the cytoplasm," explained Méndez. “This is the first study that characterizes how this process is regulated during the cell cycle for a protein that binds and regulates the translation of a family of mRNAs, and it paves the way for testing other families," he added.
 
The other idea is that only proteins with disordered regions can make such droplets. The majority of human proteins do have regions of disorder. "Evolution has selected disordered regions probably because they confer dynamics and versatility to proteins--greater speed to assemble and disassemble interactions--which is advantageous for signaling," explained Xavier Salvatella, a molecular biophysics and disordered proteins specialist at IRB Barcelona.
 
"These proteins are not freely floating around the cytoplasm but group in a certain way to form compartments, in a kind of order that enables them to perform cell functions. This is why the increasingly more precise description of these membrane-less organelles is so important in biology," the researchers added. Continuing work focuses on how these droplets contribute to disease states.
 
Sources: AAAS/Eurekalert! via IRB eLife
About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
FEB 15, 2021
Genetics & Genomics
Green Tea Boosts a DNA-Repairing, Tumor-Suppressing Protein
FEB 15, 2021
Green Tea Boosts a DNA-Repairing, Tumor-Suppressing Protein
Green tea has been lauded for its medicinal qualities, though it's been difficult to show that definitively. A new study ...
MAR 03, 2021
Microbiology
Study May Explain Higher Flu Risk in Adults That Were Premature Babies
MAR 03, 2021
Study May Explain Higher Flu Risk in Adults That Were Premature Babies
Medical treatments for the care of premature babies have allowed many individuals to get through that challenge and lead ...
MAR 16, 2021
Genetics & Genomics
New Proteins Can Emerge From 'Nothing'
MAR 16, 2021
New Proteins Can Emerge From 'Nothing'
The genetic code is the basis for life, but in order for an organism to live and survive, it needs the proteins that the ...
APR 05, 2021
Neuroscience
Could a Keto Diet Treat Alzheimer's Disease?
APR 05, 2021
Could a Keto Diet Treat Alzheimer's Disease?
  Researchers from Brigham Young University have found evidence that eating a ketogenic diet- which is a diet that ...
APR 11, 2021
Cell & Molecular Biology
An Ancient Fish Is Changing Modern Textbooks
APR 11, 2021
An Ancient Fish Is Changing Modern Textbooks
Scientists have used the gar fish to learn more about the network of nerves that links our eyes to our brains. The gar i ...
APR 13, 2021
Genetics & Genomics
Skull Fossil Yields One of the Oldest Modern Human Genomes
APR 13, 2021
Skull Fossil Yields One of the Oldest Modern Human Genomes
DNA from a very old skull is changing what we know about when and where early humans lived.
Loading Comments...