Living cells depend absolutely on tubulin, a protein that forms hollow tube-like polymers, called microtubules, which form positions for moving materials inside the cell. Tubulin-based microtubule setting allows cells to move, keep things in place or move around them. When the cells divide, the microtubule fibers pull the chromosomes into new cells. Cells with defects in tubulin polymerization die.
Microtubule fibers are hollow rods made of much smaller tubulin subunits spontaneously mounted at one end of the rod, but exactly how they do it within the cramped environment of living cells has been a mystery. Now, researchers at UC Davis have discovered the mechanism that puts these blocks in place, illustrated in a new animation.
"It will change how people think about microtubular polymerization," said Jawdat Al-Bassam, Associate Professor of Molecular and Cellular Biology at UC Davis College of Biological Sciences. A paper describing the work will be published November 13th in the newspaper Elife.
The work describes snapshots of a set of domains called TOG, or Tumor Overexpressed Genes, which are captured in the act of pushing tubulin polymerization. As the name suggests, TOGs are rich in rapidly dividing cancer cells. They show a similar structure in organisms from yeasts to humans.
Yeast workers showed project researchers Stanley Nithianantham, Al-Bassam and colleagues how a protein called Alp14, with four TOG domains, accelerates tubulin polymerization in microtubules by transporting four tubulin units to the right end of a microtubule and relieves them nicely order to build the end.
Alp14 represents a group of well-preserved proteins that are essential for cellular homeostasis and division of cells found from a yeast to a human cell. It consists of a composite linked flexible linker with two TOG1 and two TOG2 domains. Add four tubular units (two per TOG domains) and form a circle of TOG layers against each other and tubulars on the outside.
When the TOG / tubular circles reach the end of a microtubule, TOG1 ends its tubulin with the growing end, destabilizes the circle so that it unfurls, placing four tubulins in order at the end. The name was chosen because the process is like equipping a folded sail on the boat in the wind.
"It's a complete surprise that it's such an orderly, coordinated process," said Al-Bassam.
When tubular units are added to the microtubule string, they extend and carry on disassociation of tubulins from TOGs. The process explains how several TOG devices speed up the tubular assembly for the first time.
The researchers follow this study of mutant protein studies in Alp14, which are designed with predicted defects in this process to test this proposed mechanism using imaging methods for dynamic tubulin assembly in and outside living cells. The researchers plan to follow up further studies of the process, including the use of cryoelectron microscopy that allows them to visualize individual protein molecules in their natural state.
Materials provided by University of California – Davis. Original written by Andy Fell. Note Content can be edited for style and length.