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Rencurel, C.

Publications and source records attributed to Rencurel, C..

2 recordsLinked to original sources

The nuclear transport receptor Impβ is a regulator of actin polymerization

Nuclear transport receptors are best known for mediating nucleocytoplasmic transport (NCT) through nuclear pore complexes. Here, we uncover an unexpected function of the primary import receptor importin-{beta} (Imp{beta}) as a direct regulator of the actin cytoskeleton. Imp{beta} associates with stress fibers and the cell cortex and promotes actin polymerization through direct interactions. Disrupting Imp{beta}-actin binding impairs stress fiber formation and suppresses cell migration well before NCT is affected. In 3D spheroids, perturbing Imp{beta} further compromises tissue integrity, as reflected in changes to nuclear curvature and ellipticity. Together, these findings identify Imp{beta} as a regulator of actin organization in both 2D and 3D contexts, revealing a direct link between the nuclear transport machinery and the cytoskeleton.

cell biology↗

Alteration of actin cytoskeletal organisation in fetal akinesia deformation sequence

Fetal akinesia deformation sequence (FADS) represents the severest form of congenital myasthenic syndrome (CMS), a diverse group of inherited disorders characterised by impaired neuromuscular transmission. Most CMS originate from defects in the muscle nicotinic acetylcholine receptor, but the underlying molecular pathogenesis is only poorly understood. Here we show that RNAi-mediated silencing of FADS-related proteins rapsyn and NUP88 in foetal fibroblasts alters organisation of the actin cytoskeleton. We show that fibroblasts from two independent FADS individuals have enhanced and shorter actin stress fibre bundles, alongside with an increased number and size of focal adhesions, with an otherwise normal overall connectivity and integrity of the actin-myosin cytoskeleton network. By proximity ligation assays and bimolecular fluorescence complementation, we show that rapsyn and NUP88 localise nearby adhesion plaques and that they interact with the focal adhesion protein paxillin. Based on these findings we propose that a respective deficiency in rapsyn and NUP88 in FADS alters the regulation of actin dynamics at focal adhesions, and thereby may also plausibly dictate myofibril organisation and contraction in skeletal muscle of FADS individuals.

cell biology↗