The nucleus is a conserved mechanosensation and mechanoresponse organelle

Abstract

Cells in vivo exist in a dynamic environment where they experience variable mechanical influences. The precise mechanical environment influences cell-cell interactions, cell-extracellular matrix interactions, and in-turn, cell morphology and cell function. Therefore, the ability of each cell to constantly and rapidly alter their behavior in response to variations in their mechanical environment is essential for cell viability, development, and function. Mechanotransduction, the process by which mechanical force is translated into a biochemical signal to activate downstream cellular responses, is thus crucial to cell function during development and homeostasis. Although much research has focused on how protein complexes at the cell cortex respond to mechanical stress to initiate mechanotransduction, the nucleus has emerged as crucial to the ability of the cell to perceive and respond to changes in its mechanical environment. This additional method for mechanosensing allows for direct transmission of force through the cytoskeleton to the nucleus, which can increase the speed at which a cell changes its transcriptional profile. This review discusses recent work demonstrating the importance of the nucleus in mediating the cellular response to internal and external force, establishing the nucleus as an important mechanosensing organelle. V C 2016 Wiley Periodicals, Inc.Key Words: nucleus; mechanotransduction; linc complex; nucleoskeleton Introduction C ells in vivo must function within the context of variable forces exerted on them by their surroundings.These forces are often external, such as the shearing forces that are generated by blood flow. Additionally, the interactions between cells with different mechanical properties are necessary for, and drive many aspects of development and tissue morphogenesis. In each case, mechanical force can act as an important signal to regulate multiple cellular processes including cell differentiation, proliferation, and survival through a process known as mechanotransduction [Pruitt et al., 2014].Most research on mechanotransduction has focused on how mechanical force is perceived, and responded to, through signaling pathways initiated at the cell surface. The signaling is induced by mechanical forces that change the three-dimensional structure of the plasma membrane, membrane-bound proteins, and associated cytoskeletal networks, to trigger a cellular response [Iskratsch et al., 2014;Pruitt, et al., 2014]. There are many cellular structures that function in sensing changes in specific aspects of the mechanical environment. These include integrin-based adhesions which mediate cell-cell matrix interactions [Atherton et al., 2015], cadherin-based adhesions which mediate cell-cell interactions [Chanet and Martin, 2014;Lecuit and Yap;, and force sensitive membrane channels, such as Trp channels and stretch sensitive ion channels [Eijkelkamp et al., 2013]. In the case of focal adhesion based mechanosensing, external mechanical stress causes integrins to undergo a conformational change...

Cell–cell junctional mechanotransduction in endothelial remodeling

“…It contains KASH (Klarsicht, Anc-1, Syne Homology)-domain proteins, such as nesprins, that span the outer nuclear membrane and interact with the cytoskeleton. Furthermore, the complex includes SUN and emerin proteins that span the inner nuclear membrane [96, 97], which, in turn, connect to the nucleoskeleton via lamins and regulate chromatin dynamics and gene expression [98]. Another recently discovered mechano-signaling pathway that biochemically couples extracellular mechanical stimuli to nuclear responses comprises the activity of Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) proteins.…”

Ctdnep1 and Eps8L2 regulate dorsal actin cables for nuclear positioning during cell migration

“…Actin organization around the nucleus is crucial for dendritic cells to migrate in 3D environments [62]. Additionally, the LINC complex displays a central role for mechanosensing and mechanotransduction, due to its function as a bridge between the cytoskeleton and the nucleus [15,18,63,64]. Nevertheless, how this LINC complex function is regulated as well as the different cellular processes where it is involved needs to be deciphered.…”

Drosophila emerins control LINC complex localization and transcription to regulate myonuclear position

“…Because the LINC complex and emerin can either directly or indirectly regulate transcriptional activity (Lee et al, 2001;Wilkinson et al, 2003;Holaska and Wilson, 2007;Navarro et al, 2016), we investigated the transcript levels of EDMD-linked genes in each mutant to determine whether nuclear Klarsicht levels changed due to altered transcription or altered protein localization. All transcript levels were the same in bocks DP01391 mutants and controls.…”