The AAA superfamily (ATPases associated with diverse cellular activities) has been linked to a wide range of cellular processes, including cell division, cytoskeleton organization, and organelle biogenesis. Spastin is a microtubule-severing AAA protein needed for cell division and intracellular vesicle transport. Chemical probes that inhibit their activities in cells on similarly fast timescales can be valuable tools to dissect dynamic mechanisms. Spastazoline is a potent and selective cell-permeable probe for spastin with an IC50 of 99 ± 18 nM for human spastin. Treating HeLa-WT cells with spastazoline for 4.5 hours (10 µM) resulted in a ~2-fold increase in the number of cells with intercellular bridges compared to DMSO control indicating that spastazoline inhibits intercellular bridge disassembly by interfering with spastin activity. In dividing HeLa-WT cells treated with Spastazoline, EGFP-spastin accumulated at chromatin within 2–4 min after cleavage furrow ingression initiation. Imaging HeLa-WT cells in anaphase treated with spastazoline (10 µM for 1 hour) also revealed GFP-spastin puncta on chromosomes[1].
Spastazoline 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HeLa cells
10 µM
1 hour
To investigate the effect of Spastazoline on nuclear envelope reformation, results showed that Spastazoline treatment prolonged the persistence of GFP-spastin puncta on chromosomes.
Nat Chem Biol. 2019 May;15(5):444-452
HeLa cells
10 µM
4.5 hours
To investigate the effect of Spastazoline on intercellular bridge disassembly, results showed that Spastazoline treatment increased the number of intercellular bridges in HeLa-WT cells but had no significant effect in HeLa-N386C cells.
Nat Chem Biol. 2019 May;15(5):444-452
NGN2 neurons
1 µM
7 hours
To evaluate the inhibitory effect of Spastazoline on the microtubule-severing enzyme spastin and its impact on neuronal morphology in NGN2 neurons. Results showed that Spastazoline treatment did not significantly alter neurite arborization length (p=0.33 vs. control) but reduced Tubb3 signal intensity.
Mol Biol Cell. 2025 Jan 1;36(1):mr1
Spastazoline 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Contusion and lateral hemisection models of spinal cord injury
Intraperitoneal injection
20 mg/kg
Immediately after SCI then every other day until the end of experiments
Spastazoline successfully reverses the FC-A-mediated locomotor recovery and nerve regeneration phenomena
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