GPR124 regulates microtubule assembly, mitotic progression, and glioblastoma cell proliferation

Glia. 2019 Aug;67(8):1558-1570. doi: 10.1002/glia.23628. Epub 2019 May 6.

Abstract

GPR124 is involved in embryonic development and remains expressed by select organs. The importance of GPR124 during development suggests that its aberrant expression might participate in tumor growth. Here we show that both increases and decreases in GPR124 expression in glioblastoma cells reduce cell proliferation by differentially altering the duration mitotic progression. Using mass spectrometry-based proteomics, we discovered that GPR124 interacts with ch-TOG, a known regulator of both microtubule (MT)-plus-end assembly and mitotic progression. Accordingly, changes in GPR124 expression and ch-TOG similarly affect MT assembly measured by real-time microscopy in cells. Our study describes a novel molecular interaction involving GPR124 and ch-TOG at the plasma membrane that controls glioblastoma cell proliferation by modifying MT assembly rates and controlling the progression of distinct phases of mitosis.

Keywords: G protein-coupled receptors and microtubules; cell proliferation; glioblastomas.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Brain / metabolism
  • Brain Neoplasms / metabolism*
  • Cell Membrane / metabolism
  • Cell Proliferation / physiology*
  • Cells, Cultured
  • Female
  • Gene Expression
  • Glioblastoma / metabolism*
  • Humans
  • Male
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / metabolism*
  • Middle Aged
  • Mitosis / physiology*
  • Receptors, G-Protein-Coupled / metabolism*

Substances

  • ADGRA2 protein, human
  • CKAP5 protein, human
  • Microtubule-Associated Proteins
  • Receptors, G-Protein-Coupled