bims-micesi 2023-10-01 papers

Issue of 2023–10–01
three papers selected by
Valentina Piano, Uniklinik Köln

Open Biol. 2023 Sep;13(9): 230125

The signalling lipid PI3,5P2 is essential for timely mitotic exit.

Mariam Huda, Seyma Nur Bektas, Baris Bekdas, Ayse Koca Caydasi.

Coordination of mitotic exit with chromosome segregation is key for successful mitosis. Mitotic exit in budding yeast is executed by the mitotic exit network (MEN), which is negatively regulated by the spindle position checkpoint (SPOC). SPOC kinase Kin4 is crucial for SPOC activation in response to spindle positioning defects. Here, we report that the lysosomal signalling lipid phosphatidylinositol-3,5-bisphosphate (PI3,5P2) has an unanticipated role in the timely execution of mitotic exit. We show that the lack of PI3,5P2 causes a delay in mitotic exit, whereas elevated levels of PI3,5P2 accelerates mitotic exit in mitotic exit defective cells. Our data indicate that PI3,5P2 promotes mitotic exit in part through impairment of Kin4. This process is largely dependent on the known PI3,5P2 effector protein Atg18. Our work thus uncovers a novel link between PI3,5P2 and mitotic exit.

Keywords: PI3; mitosis; mitotic exit; mitotic exit network; phosphoinositide; signalling lipid

DOI: https://doi.org/10.1098/rsob.230125

Trends Genet. 2023 Sep 27. pii: S0168-9525(23)00220-2. [Epub ahead of print]

An updated view of the kinetochore architecture.

Mariko Ariyoshi, Tatsuo Fukagawa.

The kinetochore is a supramolecular complex that facilitates faithful chromosome segregation by bridging the centromere and spindle microtubules. Recent functional and structural studies on the inner kinetochore subcomplex, constitutive centromere-associated network (CCAN) have updated our understanding of kinetochore architecture. While the CCAN core establishes a stable interface with centromeric chromatin, CCAN organization is dynamically altered and coupled with cell cycle progression. Furthermore, the CCAN components, centromere protein (CENP)-C and CENP-T, mediate higher-order assembly of multiple kinetochore units on the regional centromeres of vertebrates. This review highlights new insights into kinetochore rigidity, plasticity, and clustering, which are key to understanding temporal and spatial regulatory mechanisms of chromosome segregation.

Keywords: CCAN; centromere; chromosome segregation; cluster; kinetochore; oligomerization

DOI: https://doi.org/10.1016/j.tig.2023.09.003

bioRxiv. 2023 Sep 12. pii: 2023.09.11.557210. [Epub ahead of print]

Clustering of cortical dynein regulates the mechanics of spindle orientation in human mitotic cells.

Maya I Anjur-Dietrich, Vicente Gomez Hererra, Reza Farhadifar, Haiyin Wu, Holly Merta, Shirin Bahmanyar, Michael J Shelley, Daniel J Needleman.

The forces which orient the spindle in human cells remain poorly understood due to a lack of direct mechanical measurements in mammalian systems. We use magnetic tweezers to measure the force on human mitotic spindles. Combining the spindle's measured resistance to rotation, the speed it rotates after laser ablating astral microtubules, and estimates of the number of ablated microtubules reveals that each microtubule contacting the cell cortex is subject to ∼1 pN of pulling force, suggesting that each is pulled on by an individual dynein motor. We find that the concentration of dynein at the cell cortex and extent of dynein clustering are key determinants of the spindle's resistance to rotation, with little contribution from cytoplasmic viscosity, which we explain using a biophysically based mathematical model. This work reveals how pulling forces on astral microtubules determine the mechanics of spindle orientation and demonstrates the central role of cortical dynein clustering.
Highlights: Cytoplasmic viscosity does not determine the spindle's resistance to rotationEach astral microtubule that contacts the cell cortex is pulled on by a single dynein motorPulling forces on astral microtubules determine the mechanics of spindle orientationThe mechanics of spindle orientation is regulated by clustering of dynein motors at the cell cortex.

DOI: https://doi.org/10.1101/2023.09.11.557210