<p>In conditions of microgravity the human body undergoes extensive alterations in physiological function. However, it has proven challenging to determine how these changes are mediated at the molecular and cellular level. Here, we investigated whether ELKIN1, a mechanically activated ion channel, regulates changes in cellular and molecular structures in conditions of simulated microgravity. Deletion of ELKIN1 inhibited the simulated microgravity-induced alterations of cellular structure and attachment. In addition, cells lacking ELKIN1 did not exhibit changes in focal adhesion structures and redistribution of the YAP1 transcription factor in response to simulated microgravity, consistent with wild type cells. Finally, melanoma cell invasion of a collagen gel, from organotypic spheroids, was reduced in simulated microgravity, in an ELKIN1 dependent manner. Thus, the force sensing molecule, ELKIN1, modulates the impact of microgravity at both the molecular and cellular levels, revealing one of the molecular mechanisms that underpins cellular adaptations to conditions of microgravity.</p>

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The mechanosensitive channel ELKIN1 regulates cellular adaptations to simulated microgravity

  • Daphne Wang,
  • Giulia Silvani,
  • Lioba Schroeter,
  • Remi Brynn,
  • Joshua Chou,
  • Kate Poole

摘要

In conditions of microgravity the human body undergoes extensive alterations in physiological function. However, it has proven challenging to determine how these changes are mediated at the molecular and cellular level. Here, we investigated whether ELKIN1, a mechanically activated ion channel, regulates changes in cellular and molecular structures in conditions of simulated microgravity. Deletion of ELKIN1 inhibited the simulated microgravity-induced alterations of cellular structure and attachment. In addition, cells lacking ELKIN1 did not exhibit changes in focal adhesion structures and redistribution of the YAP1 transcription factor in response to simulated microgravity, consistent with wild type cells. Finally, melanoma cell invasion of a collagen gel, from organotypic spheroids, was reduced in simulated microgravity, in an ELKIN1 dependent manner. Thus, the force sensing molecule, ELKIN1, modulates the impact of microgravity at both the molecular and cellular levels, revealing one of the molecular mechanisms that underpins cellular adaptations to conditions of microgravity.