Mechanobiology of the mammalian nuclear envelope

The nuclear envelope is a mechanosensitive structure per se, as its overall shape and invaginations are remodeled by mechanical signals. In addition, it contains important mechanosensitive macromolecular structures, such as the lamina, the LINC complex and the nuclear pore complex (NPC). These systems sense, transduce and/or respond to mechanical signals, leading to nuclear and cellular mechanoadaptation, and are important in multiple cellular processes, such as cell migration, proliferation and differentiation, cell contraction, inflammatory and innate immune responses, and the regulation of aging. However, it is becoming clear that nuclear envelope mechanobiology is complex and requires additional mechanosensitive or mechanoresponsive systems to deal with the many processes occurring at the nuclear envelope.
   In recent years, the importance of the nuclear envelope in nuclear and cellular mechanotransduction has been further established (Echarri A. Biomolecules 2022). We have recently shown that at least one nuclear import factor, named Imp7, is highly mechanoresponsive, and is essential for the crossing of the nuclear envelope of different mechanoresponsive transcriptional regulators (García-García et al., Nature Communications, 2022). Using bioinformatic and quantitative proteomic approaches we have identified several proteins that respond to mechanical signals, some of which are localized to the nuclear envelope and are barely studied. This research line aims to characterize these proteins and understand their function in cell and nuclear mechanoadaptation (right panel). To do this, we will use a combination of molecular biology and biochemistry techniques, functional genetics and approaches based on different omics (left panel), so that we can provide a deep understanding of their cellular function.