Synthetic Par Polarity Induces Cytoskeleton Asymmetry in Unpolarized Mammalian Cells

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2023 Sep 29

PMID 37774705

Authors

Joseph L Watson

Lara K Kruger

Ariel J Ben-Sasson

Alice Bittleston

Marta N Shahbazi

Vicente Jose Planelles-Herrero

Joseph E Chambers

James D Manton

David Baker

Emmanuel Derivery

Affiliations

Soon will be listed here.

Abstract

Polarized cells rely on a polarized cytoskeleton to function. Yet, how cortical polarity cues induce cytoskeleton polarization remains elusive. Here, we capitalized on recently established designed 2D protein arrays to ectopically engineer cortical polarity of virtually any protein of interest during mitosis in various cell types. This enables direct manipulation of polarity signaling and the identification of the cortical cues sufficient for cytoskeleton polarization. Using this assay, we dissected the logic of the Par complex pathway, a key regulator of cytoskeleton polarity during asymmetric cell division. We show that cortical clustering of any Par complex subunit is sufficient to trigger complex assembly and that the primary kinetic barrier to complex assembly is the relief of Par6 autoinhibition. Further, we found that inducing cortical Par complex polarity induces two hallmarks of asymmetric cell division in unpolarized mammalian cells: spindle orientation, occurring via Par3, and central spindle asymmetry, depending on aPKC activity.

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