Xk-related protein 8 regulates myoblast differentiation and survival

FEBS J. 2017 Nov;284(21):3575-3588. doi: 10.1111/febs.14261. Epub 2017 Sep 28.

Abstract

Xk-related protein 8 (Xkr8) is a scramblase and responsible for phosphatidylserine (PS) exposure on the cell surface in a caspase-dependent manner. Although PS exposure is found to be important for myotube formation during myoblast differentiation, the role of Xkr8 during myogenesis has not been elucidated. Here we show that Xkr8 contributes to myoblast differentiation. Xkr8 overexpression induced the formation of large myotubes during early differentiation, but this phenotype was not related to caspase-dependent cleavage of Xkr8. Furthermore, forced Xkr8 expression accelerated myoblast differentiation and conferred cell-death resistance after the induction of differentiation. Consistent with these results, Xkr8-knocked-down myoblasts exhibited impaired differentiation and more apoptotic cells during differentiation, implying the involvements of Xkr8 in the survival and proliferation of myoblasts. Taken together, the study shows Xkr8 influences myogenesis by acting as a positive regulator of terminal differentiation and myoblast survival.

Keywords: Xk-related protein 8; apoptosis; differentiation; myoblasts; scramblase.

Publication types

  • Editorial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Cell Differentiation
  • Cell Survival
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Myoblasts / cytology*
  • Myoblasts / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Membrane Proteins
  • RNA, Messenger
  • Xkr8 protein, human
  • Xkr8 protein, mouse