The Underexplored Mechanobiology of Lamin A Biogenesis and Homeostasis

Abstract

Lamin A is a major contributor to nuclear mechanics and an important mediator of mechanotransduction. While its role in regulating nuclear architecture is well established, considerably less attention has been given to how mechanical cues regulate lamin A itself. Here, we review current evidence demonstrating that lamin A homeostasis is dynamically controlled by mechanical stimulation through transcriptional, translational, and post-translational mechanisms regulating protein abundance, stability, and turnover. We further discuss emerging evidence suggesting that prelamin A maturation, a highly conserved multistep processing pathway, may represent a previously unrecognized mechanosensitive regulatory node. Recent studies challenge the canonical model of prelamin A processing and raise the possibility of alternative maturation pathways with important implications for lamin A homeostasis. We highlight current evidence, unresolved questions, and future directions, proposing that mechanical regulation of lamin A biogenesis represents an underexplored dimension of lamin mechanobiology with broad implications for development, aging, laminopathies, and mechanically driven diseases.