Nav: Home

Visualizing 'unfurling' microtubule growth

November 13, 2018

Living cells depend absolutely on tubulin, a protein that forms hollow tube-like polymers, called microtubules, that form scaffolding for moving materials inside the cell. Tubulin-based microtubule scaffolding allows cells to move, keeps things in place or moves them around. When cells divide, microtubule fibers pull the chromosomes apart into new cells. Cells with defects in tubulin polymerization die.

Microtubule fibers are hollow rods made of much smaller tubulin subunits that spontaneously assemble at one end of the rod, but exactly how they do this inside the crowded environment of living cells has been a mystery. Now researchers at UC Davis have uncovered the mechanism that puts these blocks in place, illustrated in a new animation.

"It's going to transform how people think about microtubule polymerization," said Jawdat Al-Bassam, associate professor of molecular and cellular biology in the UC Davis College of Biological Sciences. A paper describing the work appears Nov. 13 in the journal eLife.

The work describes snapshots of a set of domains called TOGs, or Tumor Overexpressed Genes, caught in the act of driving tubulin polymerization. As the name suggests, TOGs are abundant in rapidly-dividing cancer cells. They show a similar structure in organisms from yeast to people.

Working in yeast, project scientist Stanley Nithianantham, Al-Bassam and colleagues showed how a protein called Alp14, with four TOG domains, speeds up tubulin polymerization into microtubules by carrying four tubulin units to the correct end of a microtubule and neatly unloads them in the right order to build out 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 human cell. It consists of an assembly linked flexible linker with two TOG1 and two TOG2 domains. Add four tubulin units (two per TOG domain) and it forms a circle with the TOGs facing each other and tubulins on the outside.

When the TOG/tubulin circles reach the growing end of a microtubule, TOG1 docks its tubulin with the growing end, destabilizing the circle so that it unfurls, placing four tubulins in order on the end. The name was chosen because the process is like unfurling a folded sail on boat in the wind.

"It's a complete surprise that it's such an ordered, concerted process," Al-Bassam said.

As tubulins units are added to the microtubule strand, they straighten out, driving further disassociation of tubulins from TOGs. The process explains how multiple TOGs speed up tubulin assembly for the first time.

The researchers are following this work with studies of mutant proteins of Alp14 designed with predicted defects in this process to test this suggested mechanism using imaging approaches of dynamic tubulin assembly in and outside living cells. The researchers plan to follow up with further studies of the process, including using cryoelectron microscopy that allows them to visualize single protein molecules in their natural state.
-end-
Additional authors on the paper are Brian Cook, Madeleine Beans and Fei Guo at UC Davis and Fred Chang at UC San Francisco. The animation was produced by Julian Eskin of Brandeis University. The work was supported by grants from the NIH and made use of the Advanced Photon Source, a facility operated by the Argonne National Laboratory on behalf of the U.S. Department of Energy Office of Science.

University of California - Davis

Related Microtubules Articles:

A simple way to control swarming molecular machines
The swarming behavior of about 100 million molecular machines can be controlled by applying simple mechanical stimuli such as extension and contraction.
Cancer tumours form surprising connections with healthy brain cells
Anti-epileptic medicine can curb the dangerous communication and possibly be part of future treatment.
Stabilizing neuronal branching for healthy brain circuitry
Novel molecular mechanism may regulate microtubule stability, important for neuronal branching and potentially for nerve regeneration.
How microtubules branch in new directions, a first look in animals
Cell biologist Thomas Maresca and senior research fellow Vikash Verma at the University of Massachusetts Amherst say they have, for the first time, directly observed and recorded in animal cells a pathway called branching microtubule nucleation, a mechanism in cell division that had been imaged in cellular extracts and plant cells but not directly observed in animal cells.
Mystery solved about the machines that move your genes
Researchers have discovered how the chromosome-dividing spindle avoids slowdowns: congestion.
DNA origami to scale-up molecular motors
Researchers have successfully used DNA origami to make smooth-muscle-like contractions in large networks of molecular motor systems, a discovery which could be applied in molecular robotics.
A new molecular player involved in T cell activation
Scientists at Tokyo Institute of Technology have imaged live T cells to reveal the role of CLIP-170 in T-cell activation, a critical process in the immune response.
Keeping our cells stable: A closer look at microtubules
Microtubules help to regulate cell structure throughout our bodies. A group of Japanese researchers have used cryo-electron microscopy to shed light on how a certain protein keeps microtubules stable, and regulates microtubule-based transport within cells.
Solved protein puzzle opens door to new design for cancer drugs
Researchers at have solved a longstanding puzzle concerning the design of molecular motors, paving the way toward new cancer therapies.
Study: Tau does not stabilize microtubules, challenges approach to treating Alzheimer's
Though it is widely believed that tau protein stabilizes microtubules in neurons of the brain, new research suggests just the opposite: tau lengthens microtubules and keeps them dynamic.
More Microtubules News and Microtubules Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.