Dynamic regulation of LINC complex composition and function across tissues and contexts

• Published in: FEBS letters Vol. 597; no. 22; pp. 2823 - 2832
• Main Author: King, Megan C.
• Format: Journal Article
• Language: English
• Published: England 01.11.2023
• Subjects: Cell Nucleus - metabolism; complement; cytoskeleton; Cytoskeleton - metabolism; genes; LINC complex; mechanotransduction; Mechanotransduction, Cellular - physiology; Microtubules - metabolism; Nuclear Envelope; nuclear lamina; Nuclear Matrix - metabolism; nuclear membrane; protein metabolism; LINC complex; nuclear envelope; nuclear lamina; cytoskeleton; mechanotransduction
• ISSN: 0014-5793; 1873-3468; 1873-3468
• DOI: 10.1002/1873-3468.14757

The concept of mechanotransduction to the nucleus through a direct force transmission mechanism has fascinated cell biologists for decades. Central to such a mechanism is the linker of nucleoskeleton and cytoskeleton (LINC) complex, which spans the nuclear envelope to couple the cytoplasmic cytoskeleton to the nuclear lamina. In reality, there is not one LINC complex identity, but instead, a family of protein configurations of varied composition that exert both shared and unique functions. Regulated expression of LINC complex components, splice variants, and mechanoresponsive protein turnover mechanisms together shape the complement of LINC complex forms present in a given cell type. Disrupting specific gene(s) encoding LINC complex components therefore gives rise to a range of organismal defects. Moreover, evidence suggests that the mechanical environment remodels LINC complexes, providing a feedback mechanism by which cellular context influences the integration of the nucleus into the cytoskeleton. In particular, evidence for crosstalk between the nuclear and cytoplasmic intermediate filament networks communicated through the LINC complex represents an emerging theme in this active area of ongoing investigation. This review highlights recent advances in our understanding of the diversity of linker of nucleoskeleton and cytoskeleton (LINC) complexes, the mechanisms that regulate their structure and function, and how they contribute to tissue biology.