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CLASPs stabilize the pre-catastrophe intermediate state between microtubule growth and shrinkage
Elizabeth J Lawrence1, Saptarshi Chatterjee1, Marija Zanic1,2,3
1Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.
The Journal of Cell Biology
|May 15, 2023
Summary
Cytoplasmic linker-associated proteins (CLASPs) surprisingly promote microtubule depolymerization in some conditions. These proteins stabilize the pre-catastrophe state, ultimately suppressing microtubule catastrophe.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Cytoplasmic linker-associated proteins (CLASPs) are crucial regulators of microtubule dynamics.
- CLASPs are known to stabilize microtubules, suppressing catastrophe and promoting rescue.
- The precise mechanism by which CLASPs modulate microtubule transitions remains unclear.
Purpose of the Study:
- To investigate the effects of CLASPs on the pre-catastrophe intermediate state of microtubule dynamics.
- To elucidate how CLASPs modulate microtubule transitions at a molecular level.
Main Methods:
- Utilized distinct microtubule substrates to mimic the pre-catastrophe intermediate state.
- Examined the nucleotide-dependent activity of CLASP1 and CLASP2 family members.
- Investigated the role of a minimal TOG2-domain construct.
Main Results:
- CLASP1 promoted depolymerization of stabilized microtubules in the presence of GTP, but not without nucleotide.
- This depolymerization activity was conserved in CLASP2 family members and a TOG2-domain construct.
- CLASP1 stabilized unstable microtubules upon tubulin dilution in a GTP-dependent manner.
- CLASP1 induced microtubule substrates of varying stabilities into a common, slowly depolymerizing state.
Conclusions:
- CLASPs stabilize the pre-catastrophe intermediate state of microtubule dynamics.
- This stabilization of the intermediate state is the mechanism by which CLASPs suppress microtubule catastrophe.
- The activity of CLASPs is nucleotide-dependent and influences microtubule stability.
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