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A perinuclear actin cap regulates nuclear shape.

Shyam B Khatau¹, Christopher M Hale, P J Stewart-Hutchinson

¹Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.

Proceedings of the National Academy of Sciences of the United States of America

|October 24, 2009

Summary

This summary is machine-generated.

Cellular nuclear shape is regulated by cell adhesion geometry via an actin cap. This mechanism is disrupted in diseases like progeria and muscular dystrophy, impacting nuclear morphology.

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Area of Science:

Cell Biology
Biophysics
Disease Mechanisms

Background:

Nuclear morphology defects are linked to diseases such as cancer, progeria, cardiomyopathy, and muscular dystrophy.
The precise mechanisms governing nuclear shape control within cells remain largely unknown.

Purpose of the Study:

To elucidate the mechanism by which cells regulate nuclear shape.
To investigate the role of cell adhesion geometry in nuclear shape determination.

Main Methods:

Utilized adhesive micropatterned surfaces to precisely control fibroblast cell shape and adhesion.
Investigated the structure and dynamics of the actin cytoskeleton, particularly the perinuclear actin cap.
Examined the function of LINC complexes and actomyosin contractility in nuclear shape regulation.
Analyzed cells from mouse models of progeria and muscular dystrophy with known nuclear morphology defects.

Main Results:

Cell nucleus shape is tightly regulated by underlying cell adhesion geometry.
A dome-like actin cap, composed of contractile actin filament bundles with phosphorylated myosin, covers the nucleus and dictates its shape.
Inhibition of actomyosin contractility or disruption of LINC complexes disorganizes the actin cap and alters nuclear shape.
The actin cap's organization and nuclear shape-determining function are impaired in progeria and muscular dystrophy cells with altered A-type lamins.

Conclusions:

The perinuclear actin cap is a key mediator of nuclear shape regulation, influenced by cell adhesion.
Disruptions in this actin cap mechanism contribute to nuclear abnormalities observed in aging and muscular dystrophy.
Highlights the interplay between cell shape, nuclear shape, and cell adhesion through the actin cap.