Scientists have taken a huge leap in understanding how cells manage to keep themselves clean and healthy
Our bodies have natural tendencies to eliminate the waste generated inside them. Likewise, cells do the same. Scientists have taken a huge leap in understanding how cells manage to do the needful. How cells keep themselves clean and healthy. We all know that the cleaning job is headed with the help of phagosomes.
In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells. Phagosomes have membrane-bound proteins to recruit and fuse with lysosomes to form mature phago lysosomes.
The lysosomes contain hydrolytic enzymes and reactive oxygen species (ROS) which kill and digest the pathogens. Scientists all around the world have taken an important step in understanding this. One way that our bodies clean out toxic debris and damaged cell components is by a process called autophagy, which means ‘self-eating’.
Our cells create internal ‘recycling bins’ called autophagosomes that collect diseased, dead, or worn-out cell parts, strips them for useful bits, and uses the resulting molecules for energy to make new healthy cell parts. When this disposal system stops working properly, it can lead to cancer and diseases like Alzheimer’s and Parkinson’s.
Scientists have revealed a pathway which is supposed to control autography, which can prove to be very useful in the near future. The team had previously shown that in starved cells that need to recycle nutrients for energy, an important protein required for autophagy, GABARAP, moves from the centrosome — part of the cell that contains structural scaffolds that maintain its shape and enable cell division and movement — to the autophagosome.
In this study, they used visual markers and biochemical tools to see how the autophagy protein gets to where it needs to be. They found that a protein called PCM1 forms a compartment or ‘centriolar satellite’ which shuttles the autophagy protein from the centrosome to the autophagosome along a scaffold, a bit like a train carriage transporting a person along a railway track.
When they deleted the PCM1 gene, the GABARAP autophagy protein’s journey to the autophagosome became disorganized. Some GABARAP was degraded by an alternative recycling bin in the cell — the proteasome — and some GABARAP went to different autophagosomes from normal, highlighting the importance of PCM1 in controlling the assembly of the autophagy cell machinery.
“The identification of this new type of autophagosome formed by the disorganized GABARAP tells us that there are unique types of autophagosomes in the cell but we don’t yet understand how they would work to prevent disease,” says Sharon Tooze, Group Leader at the Francis Crick Institute. “One of the aims of our ongoing research is to manipulate this pathway, to boost cells’ ability to keep themselves clean and healthy.”
Justin Joachim, post-doctoral fellow at the Francis Crick Institute and first named author of the paper adds: “Our work reveals a previously unknown connection between the centrosome, cell division, shuttle proteins and autophagy and establishes a new regulatory pathway to control autophagy,”
The paper ‘Centriolar satellites control GABARAP ubiquitination and GABARAP-mediated autophagy’ is published in Current Biology.
This discovery can lead to a bright future of closer understanding of a cell.
Justin Joachim, Minoo Razi, Delphine Judith, Martina Wirth, Emily Calamita, Vesela Encheva, Brian D. Dynlacht, Ambrosius P. Snijders, Nicola O’Reilly, Harold B.J. Jefferies, Sharon A. Tooze. Centriolar Satellites Control GABARAP Ubiquitination and GABARAP-Mediated Autophagy. Current Biology, 2017; DOI: 10.1016/j.cub.2017.06.021