4.4 Article

Understanding the role of mechanics in nucleocytoplasmic transport

Journal

APL BIOENGINEERING
Volume 6, Issue 2, Pages -

Publisher

AIP Publishing
DOI: 10.1063/5.0076034

Keywords

-

Funding

  1. Spanish Ministry of Science and Innovation [PID2019-110298GB-I00]
  2. European Commission [H2020-FETPROACT-01-2016-731957]
  3. Generalitat de Catalunya [2017-SGR-1602]
  4. Fundacio la Marato de TV3 [201936-30-31]
  5. la Caixa Foundation [LCF/PR/HR20/52400004, LCF/BQ/DE18/11670010]
  6. Cancer Research U.K. [FC001002]
  7. U.K. Medical Research Council [FC001002]
  8. Wellcome Trust [FC001002]
  9. BBSRC sLOLA [BB/V003518/1]
  10. Leverhulme Trust Research Leadership Award [RL 2016-015]
  11. Royal Society Wolfson Fellowship [RSWF/R3/183006]
  12. Severo Ochoa Award of Excellence from MINCIN
  13. Wellcome Trust Investigator Award [212218/Z/18/Z]
  14. prize ICREA Academia for excellence in research
  15. Wellcome Trust [212218/Z/18/Z] Funding Source: Wellcome Trust
  16. BBSRC [BB/V003518/1] Funding Source: UKRI

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Cell nuclei are affected by mechanical forces, especially through the mechanical regulation of nucleocytoplasmic transport mediated by nuclear pore complexes. Mechanical forces can increase the permeability of nuclear pore complexes by exerting force on the nucleus, and the mechanical properties of transported proteins can also regulate the rate of nucleocytoplasmic transport.
Cell nuclei are submitted to mechanical forces, which in turn affect nuclear and cell functions. Recent evidence shows that a crucial mechanically regulated nuclear function is nucleocytoplasmic transport, mediated by nuclear pore complexes (NPCs). Mechanical regulation occurs at two levels: first, by force application to the nucleus, which increases NPC permeability likely through NPC stretch. Second, by the mechanical properties of the transported proteins themselves, as mechanically labile proteins translocate through NPCs faster than mechanically stiff ones. In this perspective, we discuss this evidence and the associated mechanisms by which mechanics can regulate the nucleo-cytoplasmic partitioning of proteins. Finally, we analyze how mechanical regulation of nucleocytoplasmic transport can provide a systematic approach to the study of mechanobiology and open new avenues both in fundamental and applied research. (C) 2022 Author(s).

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