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Biology subjects

Ali, N. N.

Publications and source records attributed to Ali, N. N..

2 recordsLinked to original sources

Spindle-localized F-actin regulates polar MTOC organization and the fidelity of meiotic spindle formation

Mammalian oocytes are notoriously prone to chromosome segregation errors leading to aneuploidy. The spindle provides the machinery for accurate chromosome segregation during cell division. Mammalian oocytes lack centrioles and, therefore, the meiotic spindle relies on the organization of numerous acentriolar microtubule organizing centers into two poles (polar MTOCs, pMTOCs). The traditional view is that, in mammalian oocytes, microtubules are the sole cytoskeletal component responsible for regulating pMTOC organization and spindle assembly. We identified a novel F-actin pool that surrounds pMTOCs, forming F-actin cage-like structure. We demonstrated that F-actin localization on the spindle depends on unconventional myosins X and VIIb. Selective disruption of spindle-localized F-actin, using myosin X/VIIb knockdown oocytes or photoswitchable Optojasp-1, perturbed pMTOC organization, leading to unfocused spindle poles and chromosome missegregation. Here, we unveil an important function of F-actin in regulating pMTOC organization, a critical process for ensuring the fidelity of meiotic spindle formation and proper chromosome segregation.

cell biology↗

The Scribble/SGEF/Dlg1 complex regulates the stability of apical junctions in epithelial cells

SGEF, a RhoG specific GEF, can form a ternary complex with the Scribble polarity complex proteins Scribble and Dlg1, which regulates the formation and maintenance of adherens junctions and barrier function of epithelial cells. Notably, silencing SGEF results in a dramatic downregulation of the expression of both E-cadherin and ZO-1. However, the molecular mechanisms involved in the regulation of this pathway are not known. Here, we describe a novel signaling pathway governed by the Scribble/SGEF/Dlg1 complex. Our results show that an intact ternary complex is required to maintain the stability of the apical junctions, the expression of ZO-1, and TJ permeability. In contrast, only SGEF is necessary to regulate E-cadherin expression. The absence of SGEF destabilizes the E-cadherin/catenin complex at the membrane, triggering a positive feedback loop that exacerbates the phenotype through the repression of E-cadherin transcription in a process that involves the internalization of E-cadherin by endocytosis, {beta}-catenin signaling and the transcriptional repressor Slug.

cell biology↗