A synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin

Area of Science:

• Cell Biology
• Molecular Biology
• Evolutionary Biology

Background:

• Kinesin motor domains define kinesin families.
• Kinesin-13 family members are essential microtubule depolymerizers.
• Kinesin-13s regulate microtubule dynamics in cell division and development.

Purpose of the Study:

• To investigate the evolutionary origins of microtubule depolymerization activity.
• To reconstruct and analyze a synthetic ancestral kinesin-13 motor domain.

Main Methods:

• Phylogenetic inference to predict the ancestral kinesin-13 sequence.
• Biochemical assays to measure microtubule depolymerization rates.
• Analysis of depolymerization activity on stabilized microtubules.

Main Results:

• The ancestral kinesin-13 motor domain exhibits exceptionally high microtubule depolymerization activity.
• This ancestral motor depolymerizes microtubules faster than known kinesin-13s, including MCAK.
• It can depolymerize doubly stabilized microtubules and induce internal breaks.

Conclusions:

• The ancestor of the kinesin-13 family was a potent 'super depolymerizer'.
• Kinesin-13 family members have evolved reduced depolymerization activity for controlled cellular functions.
• Evolution has refined microtubule depolymerization from extreme to regulated activity.