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Iva Tolić

Iva Tolić

@ivatolic.bsky.social

480 followers 600 following 37 posts

Biophysics of mitosis / mitotic spindle / chromosome segregation and aneuploidy Head of Laboratory of Cell Biophysics at @institutrb.bsky.social, previously at @mpi-cbg.de, LENS Florence, Niels Bohr Institute, @hsph.harvard.edu, Uni Zagreb. tolic.irb.hr

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Iva Tolić @ivatolic.bsky.social · 6d

A golden Zagreb morning before work

Iva Tolić @ivatolic.bsky.social · 8d

Congrats @krunovuk.bsky.social on this remarkable work! Thanks @erc.europa.eu, www.hrzz.hr, and www.srce.unizg.hr for supporting us!

Iva Tolić @ivatolic.bsky.social · 8d

We propose a kinetochore-centrosome feedback mechanism controlling chromosome movement: chromosomes near centrosomes rely on CENP-E because high Aurora A activity boosts Aurora B at kinetochores, restricting end-on attachments. CENP-E counteracts this by downregulating Aurora B.

Iva Tolić @ivatolic.bsky.social · 8d

Notably, the dependence of polar chromosomes on CENP-E can be bypassed by using constitutively dephosphorylated Hec1, emphasizing the role of Aurora kinase-mediated Hec1 phosphorylation in preventing congression when CENP-E is absent.

Iva Tolić @ivatolic.bsky.social · 8d

Does Aurora A at spindle poles directly promote Aurora B activity at kinetochores? Yes, our results show that acute inhibition of Aurora A reduces Aurora B activity at polar kinetochores, accompanied by a decrease in the number of polar chromosomes.

Iva Tolić @ivatolic.bsky.social · 8d

At poles that contain centrioles, high Aurora A kinase enhances Aurora B activity on kinetochores of polar chromosomes, increasing phosphorylation of microtubule-binding proteins and preventing stable microtubule attachments in the absence of CENP-E.

Iva Tolić @ivatolic.bsky.social · 8d

Centrosomes inhibit the initiation of congression in the absence of CENP-E, and depletion of centrioles allows chromosomes near acentriolar poles to initiate congression independently of CENP-E.

Iva Tolić @ivatolic.bsky.social · 8d

In our second paper, we asked why only polar chromosomes depend on CENP-E for congression. We inhibited Plk4 to generate spindles where one pole had centrioles and the other did not. Strikingly, the acentriolar pole (on the right in the movie) rarely had polar chromosomes.

Iva Tolić @ivatolic.bsky.social · 8d

And now… part two of our twin papers on how chromosomes find their place before division! Led by @krunovuk.bsky.social at @institutrb.bsky.social, out in @natcomms.nature.com!

doi.org/10.1038/s414...
doi.org/10.1038/s414...

Missed the thread on the first paper? Catch up:
bsky.app/profile/ivat...

Iva Tolić @ivatolic.bsky.social · 16d

In sum, the first paper shows that chromosome congression is coupled with biorientation, with CENP-E linking the two. A thread on the second paper is coming soon! Congrats @krunovuk.bsky.social on this amazing work! We appreciate support from @erc.europa.eu, www.hrzz.hr, and www.srce.unizg.hr.

Iva Tolić @ivatolic.bsky.social · 16d

We propose that congression operates as a negative feedback loop between the activity of Aurora kinases that oppose congression by destabilizing end-on attachments, but also activate CENP-E, which then promotes congression by opposing the activity of Aurora kinases.

Iva Tolić @ivatolic.bsky.social · 16d

In our model, stabilization of end-on attachments without CENP-E is delayed due to Aurora kinase-mediated phosphorylation of microtubule-binding proteins and expansion of the fibrous corona, which obstructs attachments. CENP-E counters this by reducing phosphorylation.

Iva Tolić @ivatolic.bsky.social · 16d

Why can’t kinetochores start their movement without CENP-E? Is dynein holding them? No. This is due to Aurora kinases that oppose the formation of end-on attachments near the spindle poles. When Aurora B is inhibited in the absence of CENP-E, kinetochores start to move!

Iva Tolić @ivatolic.bsky.social · 16d

To directly test if congression is coupled with biorientation, we performed STED super-resolution imaging. Indeed, reactivation of CENP-E led to a gradual transition from lateral to end-on attachments on polar chromosomes.

Iva Tolić @ivatolic.bsky.social · 16d

Chromosome congression involves progressive capture and stabilization of end-on microtubule attachments, based on recruitment of the attachment marker Astrin, together with a gradual reduction of SAC and fibrous corona proteins on kinetochores.

Iva Tolić @ivatolic.bsky.social · 16d

We found that without CENP-E kinetochores move in the same manner as normally, just not as frequently. Thus, CENP-E is not required for chromosome movement during congression, challenging the current view, but instead for the initiation of this movement.

Iva Tolić @ivatolic.bsky.social · 16d

@krunovuk.bsky.social pushed the limits of long-term live-cell imaging by simultaneously imaging hundreds of cells for 24 h using lattice light-sheet microscopy. By adding chemical inhibitors, he tested a time-resolved hierarchy of molecular networks working during congression.

Iva Tolić @ivatolic.bsky.social · 16d

Do you know how chromosomes travel to the spindle midplane in mitosis? The motor protein CENP-E is crucial for this. Without it, some chromosomes stay trapped at the poles. The current model says it glides kinetochores along microtubules... but does it really?

Iva Tolić @ivatolic.bsky.social · 16d

Two back-to-back stories on mitosis led by my incredible postdoc @krunovuk.bsky.social at @institutrb.bsky.social, in which we challenge the gliding model of CENP-E-driven chromosome congression! Today in @natcomms.nature.com
doi.org/10.1038/s414...
doi.org/10.1038/s414...

Reposted by Iva Tolić

GdR ImaBio @gdrimabio.bsky.social · Oct 5

#Mifobio2025

Focus on the module 5:
👉 Physical measurements, control and handling -Mechanobiology

We are delighted to welcome Professor @ivatolic.bsky.social
Ruđer Bošković Institute

Lecture : “Mechanobiology of the Mitotic Spindle”

👉 imabio-cnrs.fr

#GDRimabio #microscopy #biological_imaging

Reposted by Iva Tolić

GdR ImaBio @gdrimabio.bsky.social · Oct 3

🔬For 22 years, we have been organizing #Mifobio "Functional Microscopy for Biology" the @cnrs.fr thematic school.

🎓 Courses, Seminars, Round Tables, Workshops. The overall theme concerns #biological_imaging in its most interdisciplinary aspects.

👉 Program: imabio-cnrs.fr

#GDRImaBio #Mifobio2025

Iva Tolić @ivatolic.bsky.social · Sep 10

Wonderful, Pavel, congrats!!! 🍸🍸

Reposted by Iva Tolić

Adrian Saurin @adesaurin.bsky.social · Jul 3

Delighted to share our latest work showing how cells that evade #senescence after CDK4/6 inhibition are primed to become aneuploid because of their increased size (due to defects in cohesion and the mitotic checkpoint). Great work by fab PhD student Aanchal Pareri 👏🧪

www.biorxiv.org/content/10.1...

Cell enlargement causes mitotic errors and aneuploidy in cells that evade senescence after CDK4/6 inhibition

CDK4/6 inhibitors (CDK4/6i) arrest the cell cycle in G1 leading to cellular overgrowth and p53-dependent senescence. They are used to treat metastatic HR+/HER2- breast cancer, but resistance is common...

www.biorxiv.org

Iva Tolić @ivatolic.bsky.social · Apr 26

Amazing energy at our second Swiss-Croatian Bilateral Project meeting with @labmeraldi.bsky.social and Pavin Group in Srebreno near Dubrovnik! The labs teamed up instantly, with lots of brainstorming and cool ideas for new joint projects! #HRZZ @snsf-ch.bsky.social
🇭🇷🇨🇭

Iva Tolić @ivatolic.bsky.social · Apr 8

Great memories from the joint meeting with the Meraldi Lab and Pavin Group last year in Split! Can't wait for this year's meeting, which starts tomorrow! Excited for more cool science through our Swiss-Croatian Bilateral Project #HRZZ @snsf-ch.bsky.social 🇭🇷🇨🇭