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Miles, C. E.

Publications and source records attributed to Miles, C. E..

2 recordsLinked to original sources

kSHREC ‘Delta’ reflects the shape of kinetochore rather than intrakinetochore tension

Distance between fluorescent spots formed by various kinetochore proteins ( Delta) is proposed to reflect the level of intrakinetochore tension (IKT). However, larger-scale changes in the kinetochore architecture may also affect Delta. To test this possibility, we measure Delta in long kinetochores of Indian muntjac (IM) whose shape, size, and orientation are discernable in conventional light microscopy. We find that architecture of IM kinetochores and the value of Delta change minimally when microtubule-mediated forces are suppressed by Taxol. In contrast, large decreases of Delta observed in Taxol-treated human cells coincide with prominent changes in length and shape of the kinetochore. We also find that inner and outer kinetochore proteins intermix within a common spatial compartment instead of forming separate thin layers. These observations, supported by computational modelling, suggest that changes in Delta reflect changes in the kinetochore shape rather than the level of IKT.

cell biology

A unified role for membrane-cortex detachment during cell protrusion initiation

Cell morphogenesis employs a diversity of membrane protrusions. They are discriminated by differences in force generation. Actin polymerization is the best studied mechanism of force generation, but growing interest in how variable molecular conditions and microenvironments alter morphogenesis has revealed other mechanisms, including intracellular pressure. Here, we show that local depletion of membrane cortex links is an essential step in the initiation of both pressure-based and actin-based protrusions. This observation challenges the quarter-century old Brownian ratchet model of actin-driven membrane protrusion, which requires an optimal balance of actin filament growth and membrane tethering. An updated model confirms membrane-filament detachment is necessary to activate the ratchet mechanism. These findings unify the regulation of different protrusion types, explaining how cells generate robust yet flexible strategies of morphogenesis.

cell biology