Altered microglial phagocytosis in GPR34-deficient mice

Glia. 2015 Feb;63(2):206-15. doi: 10.1002/glia.22744. Epub 2014 Aug 20.

Abstract

GPR34 is a Gi/o protein-coupled receptor (GPCR) of the nucleotide receptor P2Y12 -like group. This receptor is highly expressed in microglia, however, the functional relevance of GPR34 in these glial cells is unknown. Previous results suggested an impaired immune response in GPR34-deficient mice infected with Cryptococcus neoformans. Here we show that GPR34 deficiency results in morphological changes in retinal and cortical microglia. RNA sequencing analysis of microglia revealed a number of differentially expressed transcripts involved in cell motility and phagocytosis. We found no differences in microglial motility after entorhinal cortex lesion and in response to laser lesion. However, GPR34-deficient microglia showed reduced phagocytosis activity in both retina and acutely isolated cortical slices. Our study identifies GPR34 as an important signaling component controlling microglial function, morphology and phagocytosis.

Keywords: GPCR; GPR34; OHSC; RNA sequencing; microglia; neurodegenerative disease; phagocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • CD11b Antigen / genetics
  • CD11b Antigen / metabolism
  • CX3C Chemokine Receptor 1
  • Cell Movement / genetics
  • Flow Cytometry
  • Gene Expression Regulation / genetics*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microglia / physiology*
  • Organ Culture Techniques
  • Phagocytosis / genetics*
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism
  • Receptors, Lysophospholipid / deficiency*
  • Receptors, Lysophospholipid / genetics
  • Retina / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • CD11b Antigen
  • CX3C Chemokine Receptor 1
  • Cx3cr1 protein, mouse
  • G-protein-coupled receptor 34
  • Receptors, Chemokine
  • Receptors, Lysophospholipid
  • Tumor Necrosis Factor-alpha
  • Green Fluorescent Proteins