Silencing the Cytoskeleton Protein Iba1 (Ionized Calcium Binding Adapter Protein 1) Interferes with BV2 Microglia Functioning

Cell Mol Neurobiol. 2020 Aug;40(6):1011-1027. doi: 10.1007/s10571-020-00790-w. Epub 2020 Jan 16.

Abstract

Iba1 (ionized calcium binding adapter protein 1) is a cytoskeleton protein specific only for microglia and macrophages, where it acts as an actin-cross linking protein. Although frequently regarded as a marker of activation, its involvement in cell migration, membrane ruffling, phagocytosis or in microglia remodeling during immunological surveillance of the brain suggest that Iba1 is not a simple cytoskeleton protein, but a signaling molecule involved in specific signaling pathways. In this study we investigated if Iba1 could also represent a drug target, and tested the hypothesis that its specific silencing with customized Iba1-siRNA can modulate microglia functioning. The results showed that Iba1-silenced BV2 microglia migrate less due to reduced proliferation and cell adhesion, while their phagocytic activity and P2x7 functioning was significantly increased. Our data are the proof of concept that Iba1 protein is a new microglia target, which opens a new therapeutic avenue for modulating microglia behavior.

Keywords: BV2 microglia; Iba1 protein; Migration; Phagocytosis; Proliferation; siRNA.

MeSH terms

  • Animals
  • Calcium-Binding Proteins / metabolism*
  • Cell Adhesion
  • Cell Count
  • Cell Line
  • Cell Movement
  • Cell Proliferation
  • Cytoskeletal Proteins / metabolism*
  • Gene Silencing*
  • Leukocyte Common Antigens / metabolism
  • Mice
  • Microfilament Proteins / metabolism*
  • Microglia / metabolism*
  • Opsonin Proteins / metabolism
  • Phagocytosis
  • RNA, Small Interfering / metabolism
  • Receptors, Purinergic P2X7 / metabolism
  • Reproducibility of Results
  • Zymosan / metabolism

Substances

  • Aif1 protein, mouse
  • Calcium-Binding Proteins
  • Cytoskeletal Proteins
  • Microfilament Proteins
  • Opsonin Proteins
  • RNA, Small Interfering
  • Receptors, Purinergic P2X7
  • Zymosan
  • Leukocyte Common Antigens