4.6 Review

LINCing Senescence and Nuclear Envelope Changes

Journal

CELLS
Volume 11, Issue 11, Pages -

Publisher

MDPI
DOI: 10.3390/cells11111787

Keywords

senescence; LINC complex; Nesprins; SUN; nuclear envelope

Categories

Funding

  1. Qatar Research Leadership Program scholarship from Qatar National Research Fund

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The nuclear envelope plays a crucial role in cellular organization, signaling, and survival, and is particularly important in the process of senescence. Specific proteins of the nuclear envelope, such as Lamin B1 and LINC complex proteins, have been identified as key players in senescence, and have functions beyond their role in forming the nuclear envelope. These proteins are involved in DNA repair, cell signaling, and nuclear shape regulation, all of which are important in senescence.
The nuclear envelope (NE) has emerged as a nexus for cellular organization, signaling, and survival. Beyond its role as a barrier to separate the nucleoplasm from the cytoplasm, the NE's role in supporting and maintaining a myriad of other functions has made it a target of study in many cellular processes, including senescence. The nucleus undergoes dramatic changes in senescence, many of which are driven by changes in the NE. Indeed, Lamin B1, a key NE protein that is consistently downregulated in senescence, has become a marker for senescence. Other NE proteins have also been shown to play a role in senescence, including LINC (linker of nucleoskeleton and cytoskeleton) complex proteins. LINC complexes span the NE, forming physical connections between the cytoplasm to the nucleoplasm. In this way, they integrate nuclear and cytoplasmic mechanical signals and are essential not only for a variety of cellular functions but are needed for cell survival. However, LINC complex proteins have been shown to have a myriad of functions in addition to forming a LINC complex, often existing as nucleoplasmic or cytoplasmic soluble proteins in a variety of isoforms. Some of these proteins have now been shown to play important roles in DNA repair, cell signaling, and nuclear shape regulation, all of which are important in senescence. This review will focus on some of these roles and highlight the importance of LINC complex proteins in senescence.

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