Tubby regulates microglial phagocytosis through MerTK

Nora B. Caberoy, Gabriela Alvarado, Wei Li

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Immunologically-silent microglial phagocytosis of apoptotic cells and cellular debris is critical for CNS homeostasis and innate immune balance. The beneficial and detrimental effects of microglial phagocytosis on neurons remain controversial. Phagocytosis ligands are the key to selecting extracellular cargos, initiating the engulfment process, defining phagocyte functional roles and regulating phagocyte activities with therapeutic potentials. Here we characterized tubby as a new ligand to regulate microglial phagocytosis through MerTK receptor, which is well known for its immunosuppressive signaling. Tubby at 0.1nM significantly induced microglial phagocytosis of apoptotic cells with a maximal activity at 10nM. Tubby activated MerTK with receptor autophosphorylation in a similar dose range. Excessive soluble MerTK extracellular domain blocked tubby-mediated microglial phagocytosis of plasma membrane vesicles as cellular debris. Immunocytochemistry revealed that the ingested cargos were co-localized with MerTK-dependent non-muscle myosin II, whose rearrangement is necessary for cargo engulfment. Phagosome biomarker Rab7 was colocalized with cargos, suggesting that internalized cargos were targeted to phagocytic pathway. Tubby stimulated phagocytosis by neonatal and aged microglia with similar activities, but not by MerTK-/- microglia. These results suggest that tubby is a ligand to facilitate microglial phagocytosis through MerTK for the maintenance of CNS homeostasis.

Original languageEnglish (US)
Pages (from-to)40-48
Number of pages9
JournalJournal of Neuroimmunology
Volume252
Issue number1-2
DOIs
StatePublished - Nov 14 2012

Keywords

  • Eat-me signal
  • MerTK
  • Microglia
  • Phagocytosis
  • Phagocytosis ligand
  • Tubby

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

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