AsianScientist (May 26, 2015) – Local stimulation at the cell periphery can lead to the formation of actin structures at distal sites such as the nucleus. The findings, published in the Proceedings of the National Academy of Sciences, suggest a mechanism for how mechanosensing can influence nuclear activity.
Cells, like people, can sense when forces are applied to them. Instead of buckling under the influence of external forces, cells constantly respond and adapt by altering their cytoskeleton or switching on or off biochemical signaling pathways. The cytoskeleton, which lies within the cytoplasm, is a densely interconnected network of filaments, comprised primarily of a protein known as actin.
Until now, most studies showed that such cytoskeletal reorganization occurs at regions in close proximity to where the force is applied, however it remained unclear how far such effects actually reached.
Scientists from the Mechanobiology Institute (MBI), National University of Singapore, in collaboration with scientists from the Department of Biology, New York University speculated that mechanical stimuli could reach this region primarily by actin remodeling. They tested their hypothesis using an atomic force microscopy probe to apply localized forces at the cell periphery.
The researchers discovered that localized mechanical stimulation could have distant effects on actin remodeling. Described for the first time was an actin structure that formed as a ring along the outer boundaries of the nuclear envelope. This structure, which they named the actin rim, was observed to be short-lived, disappearing when the forces were removed. The formation of the actin rim was explained by a prominent increase in actin filament assembly around the nucleus.
This was found to result from biochemical signaling. Specifically, a rapid release of calcium ions within the cytoplasm occurred immediately after the application of force. The calcium ions act as biochemical messengers that relay the force signals to an actin regulatory protein, inverted formin 2 (INF2). INF2, along with other mediators, functions to bring together actin proteins dispersed in the cytoplasm, leading to their assembly into filament structures.
This study enhances our understanding of how forces applied on a small spot on the cell surface can travel across the cell and elicit responses at distant regions. It was proposed that the actin rim could serve as a means to transport DNA-regulatory signals from the cytoplasm into the nucleus. Furthermore, the formation of the actin rim may act as a shield to protect DNA from forces and stabilize nuclear functions.
The article can be found at: Shao et al. (2015) Mechanical Stimulation Induces Formin-dependent Assembly Of A Perinuclear Actin Rim.
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Source: Mechanobiology Institute, Singapore.
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