KASH proteins transform from passive tethers to dynamic conductors of motor-driven nuclear dynamics

TL;DR

This paper explores how KASH proteins act as dynamic organizers of nuclear movement and positioning, impacting various cellular processes and diseases.

Contribution

The paper introduces a new framework highlighting KASH proteins' roles beyond structural tethers, emphasizing their regulatory and disease-related functions.

Findings

KASH proteins selectively recruit microtubule motor proteins to control nuclear dynamics.

They coordinate actin and microtubule systems for cytoskeletal interactions.

Tissue-specific regulation of KASH proteins explains diverse disease manifestations.

Abstract

Nuclear-cytoskeletal coupling orchestrates critical cellular processes from migration to tissue organization. At the core of this machinery, outer nuclear membrane Klarsicht/ANC-1/SYNE homology (KASH) proteins function as sophisticated molecular conductors rather than simple structural tethers. This review examines three principles redefining these versatile proteins: specialized interfaces for selective microtubule motor protein recruitment that orchestrate diverse chromosomal and nuclear dynamics, coordination of multiple cytoskeletal systems through simultaneous engagement with actin and microtubules, and tissue-specific regulation that explains the diverse KASH protein-related disease manifestations. This framework provides insights into conditions from muscular dystrophy to neurodegeneration and suggests targeted therapeutic opportunities.

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