Dynamic Instability: slow-growing and rapidly shrinking MT’s co-exist

GTP cap hypothesis:

· Rate of addition of GTP-tubulin to plus end depends on concentration of a, b dimers.

· Hydrolysis of GTP-b-tubulin to GDP-b-tubulin occurs after addition; rate of hydrolysis is constant.

· Rate of loss of GTP-tubulin is low but rate of loss of GDP-tubulin is 100x faster.

· Plus end with GTP-tubulin (“GTP cap”) will continue to grow but if GDP-tubulin is exposed MT will shrink rapidly due to GDP-tubulin loss.

Example 1: high concentration of GTP-tubulin dimers

rate of addition > rate of hydrolysis

plus end stabilized by large GTP cap; growth continues

Example 2: concentration of T ~ critical concentration

Rate of addition = rate of hydrolysis

Rate of addition stays just ahead of rate of hydrolysis; slow growth

Hydrolysis overtakes addition, GTP cap lost, GDP exposed; rapid loss of subunits, MT shrinks.

Example 3: Rescue

Rapidly shrinking MT

If T adds to the ends, cap is restored and growth resumes as long as addition stays ahead of hydrolysis.

As seen in video, MT’s in cells alternate between periods of slow growth and rapid shrinkage: catastrophe-rescue cycles.