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SSNA1 stabilizes dynamic microtubules and detects microtubule damage
Elizabeth J Lawrence1, Goker Arpag1, Cayetana Arnaiz1
1Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States.
Elife
|December 31, 2021
Summary
Sjögren's syndrome nuclear autoantigen-1 (SSNA1) stabilizes microtubules by slowing growth and shrinkage, and protects them from damage. This protein acts as both a stabilizer and a damage sensor in cellular structures.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- Sjögren's syndrome nuclear autoantigen-1 (SSNA1/NA14) is a microtubule-associated protein crucial for cilia, cell division, and neuronal development.
- The direct impact of SSNA1 on microtubule dynamics and stability remains largely uncharacterized.
Purpose of the Study:
- To investigate the direct effects of purified human SSNA1 on microtubule dynamics and stability in vitro.
- To determine SSNA1's interaction with microtubule ends and lattices, and its role in response to microtubule damage.
Main Methods:
- In vitro reconstitution assays using purified proteins.
- Total internal reflection fluorescence (TIRF) microscopy to visualize microtubule dynamics.
- Analysis of microtubule growth, shrinkage, catastrophe, and rescue rates.
- Assessment of SSNA1's interaction with microtubule lattice and damage sites.
- Evaluation of SSNA1's protective effect against spastin-induced microtubule severing.
Main Results:
- SSNA1 significantly modulates microtubule dynamic instability, decreasing growth and shrinkage rates, and promoting rescue.
- SSNA1 forms distinct stretches on growing microtubule ends and binds cooperatively to the microtubule lattice.
- SSNA1 accumulates at microtubule damage sites, both naturally occurring and induced by spastin.
- SSNA1 binding confers protection to microtubules against the severing activity of spastin.
Conclusions:
- SSNA1 functions as a potent microtubule-stabilizing protein.
- SSNA1 acts as a novel sensor of microtubule damage.
- These activities highlight SSNA1's critical role in maintaining microtubule structure and integrity within cells.
Keywords:
SSNA1cell biologycytoskeletonin vitro reconstitutionmicrotubule damagemicrotubule dynamicsmolecular biophysicsnonespastinstructural biologyMore Related Videos
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