08/25/2022
Newsroom in Diario da Sade
It became possible for the first time to track the proteins secreted by an organ as they spread throughout the body.
[Imagem:Â Scripps Research/University of Southern California]
How do the parts of the body communicate?
Many of our systems and bodies are in constant contact with each other. During physical exercise, for example, muscles send signals to fatty tissues and the liver requesting the energy reserves they need.
While these communication networks play an important role in our bodies every day, these pathways have historically been difficult to detect.
But an unprecedented new paradigm capable of distinguishing and tracking signaling proteins, which exchange information between agencies, promises to make it possible to create maps of these pathways.
The “model” is a genetically modified mouse that marks proteins secreted by the cell, causing it to glow, allowing scientists to track its movement throughout the animal’s body.
This new technology could reveal the molecular differences between healthy tissue and diseased tissue, as well as the role that communication between organs plays in disease initiation and progression.
protein labeling
The researchers used an enzyme, called BirA*G3, that labels proteins secreted with a biotin “label.” These biotin markers are then detected in live mice using a method called quantitative proteomics mass spectrometry, a technique used to measure proteins in a sample.
Early tests confirmed that this technology reveals where proteins originate from and where they travel in the body.
When BirA*G3 was widely activated throughout the animal body, all secreted proteins were successfully labeled, even low abundance proteins with hormone-like properties. Similarly, when only BirA*G3 was activated in the liver, only secreted proteins related to the organ system were characterized—also showing the high specificity of the model.
“Given the central role of key secreted proteins such as insulin, there is great interest in identifying novel secreted proteins,” said Professor Andrew McMahon of the University of Southern California. “Genomics studies indicate that many new proteins have yet to be characterized. We look forward to diving deep into this area now that we have validated the technology.”
disease paths
There are many research applications for this technology. For example, scientists could begin to map undiscovered disease pathways and eventually develop targeted therapies, as many diseases originate in one organ and eventually spread to others.
Cancer, with its metastatic characteristics, is an example of this.
On the other hand, studies have shown that many health complications that arise from obesity may be due to poor communication with organs, but many molecular mechanisms remain unknown.
One of the team, Ilya Drogenin, concluded, “Any protein we discover that plays a role in disease can translate into a treatment.”
Article: A genetic model for in vivo proximity labeling of mammalian secretion
Authors: secretome Rui Yang, Amanda S.Meyer, Ilia A. Droujinine, Namrata D. Udeshi, Yanhui Hu, Jinjin Guo, Jill A. McMahon, Dominique K. Carey, Charles Xu, Qiao Fang, Jihui Sha, Shishang Qin, David Rocco, James Walschlegel, Alice Y-Ting, Stephen A. Carr, Norbert Perrimon, Andrew B. McMahon
Publication: Open Biology
DOI: 10.1098 / rsob.220149