The molecular mechanism of spindle pole focusing: NuMA as a dynein adaptor and microtubule minus end regulator
Year: 2025
Type: dissertation
Abstract: This project investigates the molecular mechanisms underlying chromosome segregation during eukaryotic cell division. Specifically, it explores the role of the motor protein cytoplasmic dynein 1 in maintaining metaphase spindle integrity by clustering microtubule minus ends into focused poles. We conducted in vitro assays using purified proteins and total internal reflection fluorescence (TIRF) microscopy to show that the nuclear mitotic apparatus (NuMA) protein acts as a dynein adaptor. NuMA triggers dynein's processive motility, supported by the cofactors dynactin and lissencephaly 1 (Lis1). In addition, NuMA selectively arrests the growth of microtubule minus ends, binding preferentially to those not capped by the microtubule nucleator γ-tubulin ring complex (γTURC). It can also bind to new minus ends freshly generated by laser ablation. Finally, we showed that the dynein/dynactin/NuMA complex can transport microtubule minus ends. These findings clarify the interplay of dynein, dynactin, NuMA, and Lis1 in organizing spindle poles during cell division.
Author: Colombo, Sabina
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7110504132
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