Sachin Kotak

New Aurora A kinase role in maintaining proper nuclear shape organization at mitotic exit:
NuMA inhibition causes its dynamic-to-solid material-state transition, leading to bending of segregated mitotic chromosomes
Sachin Kotak @spindlebehavior.bsky.social et al
www.embopress.org/doi/full/10....

Hi Carlos, thank you so much!

Hi Jorge, thank you so much!

Thank you so much-Helfrid!

Huge thanks to all students for their hard work, to our collaborator @daannoordermeerlab.bsky.social for a wonderful partnership, and to colleagues/friends for valuable suggestions.
Grateful to DBT, ANRF, CEFIPRA, and IISc for their support 🙏

Finally, by tracking nucleolar organization and chromatin–chromatin contacts (via 4C analysis), we show that perturbing nuclear organization directly disrupts chromatin organization at mitotic exit. This work highlights the biological significance of spindle pole disassembly at mitotic exit.

By restricting Aurora A activity to only one spindle pole, we found that the opposite pole lacking Aurora A activity accumulates “solid” NuMA, which in turn forces the segregated chromosomes to bend around this abnormal pole.

Notably, forcing multimerization of NuMA molecules is sufficient to recapitulate the phenotype seen upon Aurora A inactivation. This indicates that multimerization is the key process disrupted when Aurora A activity is lost.

We further show that dynamic-to-solid material state transition in the absence of Aurora A activity in anaphase is assisted by glutamine residues in its C-terminus IDR.

NuMA accumulation at spindle poles depends on:
• dynein/dynactin (trucks)
• its coiled-coil domain (cranes), and
• its ability to form multivalent cation-π interactions through its intrinsically disordered region (IDR) at the C-terminus (hooks in cyan).

When Aurora A is inactivated, we found that NuMA, a conserved spindle pole protein, undergoes a material state transition from dynamic to solid, and abnormally accumulates at the spindle poles.
This abnormal “accumulation” causes NuMA segregated chromosomes/nuclei to bend around them.

- We found that Aurora A activity in anaphase is crucial for shaping the nucleus during mitotic exit.
To probe this, we built a cyclin-B1-based degron tool that enables rapid, phase-specific degradation of Aurora A, right as cells exit mitosis.

Happy to share our work in @embojournal 👉 shorturl.at/zXNyn
For decades, we’ve known cells dismantle & rebuild the nuclear envelope in sync with spindle poles. But why does this coordination matter? And how do pole material properties ensure error-free division?
Follow this thread to know more 👇

It’s happening on the 15th!!

#centrosome, #microtubules, #centromere, #mitosis, #cellbiology

@kaustuvsanyal.bsky.social
@viji-draviam.bsky.social
@spindlebehavior.bsky.social

The cover of @jcb.org's July issue (rupress.org/jcb/issue/22...) shows a confocal timelapse imaging of #Celegans one-cell embryo expressing fluorescently labeled plasma membrane, microtubules, chromosomes, and ZEN-4, a plus-end directed kinesin motor protein (Adhikary et al. doi.org/10.1083/jcb....)