Nestin Forms a Flexible Cytoskeleton by Means of a Huge Tail Domain That Is Reversibly Stretched and Contracted by Weak Forces

Ayana Yamagishi; Rina Tokuoka; Kazuki Imai; Mei Mizusawa; Moe Susaki; Koki Uchida; Saku T. Kijima; Akira Nagasaki; Daijiro Takeshita; Chiaki Yoshikawa; Taro Q. P. Uyeda; Chikashi Nakamura

doi:10.3390/cells14020138

論文 Nestin Forms a Flexible Cytoskeleton by Means of a Huge Tail Domain That Is Reversibly Stretched and Contracted by Weak Forces

Ayana Yamagishi ; Rina Tokuoka ; Kazuki Imai ; Mei Mizusawa ; Moe Susaki ; Koki Uchida ; Saku T. Kijima ; Akira Nagasaki ; Daijiro Takeshita ; Chiaki Yoshikawa ; Taro Q. P. Uyeda ; Chikashi Nakamura

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Ayana Yamagishi, Rina Tokuoka, Kazuki Imai, Mei Mizusawa, Moe Susaki, Koki Uchida, Saku T. Kijima, Akira Nagasaki, Daijiro Takeshita, Chiaki Yoshikawa, Taro Q. P. Uyeda, Chikashi Nakamura. Nestin Forms a Flexible Cytoskeleton by Means of a Huge Tail Domain That Is Reversibly Stretched and Contracted by Weak Forces. Cells. 2025, 14 (2), 138. https://doi.org/10.3390/cells14020138

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(abstract)

Nestin, a type VI intermediate filament protein, is well-known as neural stem cell marker protein. On the other hand, nestin specifically expressed in high-grade cancer cells and forms copolymerized filaments with vimentin. Our previous study has shown that nestin inhibits the binding of vimentin’s tail domain to actin microfilaments (AFs) by steric hin-drance with large nestin tail domain (NTD) of 170 kDa, thereby increasing the mobility of the three-dimensional network of the cytoskeleton, enhancing cell flexibility, and contrib-uting to cancer progression. In the course of the study, it was also discovered that nestin itself binds extremely stably to AFs via the NTD. This fact contradicts the mechanism de-scribed above. However, based on the further discovery that nestin binds to actin at the C-terminal end of NTD, we newly hypothesized that NTD forms a flexible cytoskeletal structure by extending with weak force. In vitro tensile tests using atomic force microscope were performed to assess the mechanical properties of NTDs to confirm the hypothesis. The C-terminus of the NTD was bound to the AFs by bringing the AFM tip modified with the NTD into contact with the AFs on the substrate. Tensile tests showed that the NTDs were elongated to a length corresponding to approximately 80% of their maximum length at weak forces of less than 150 pN. Furthermore, repeated tensile tests revealed that the NTD refolded quickly and behaved like a soft elastic material. Nestin stably binds to AFs and forms a three-dimensional network of the cytoskeleton, and the NTD extends with weak force and contracts quickly when the load is released. Thereby, it is suggested that nestin absorbs mechanical load on cells and plays a role in restoring the cytoskeleton.

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