GPNMB is a biomarker for lysosomal dysfunction and is secreted via LRRK2-modulated lysosomal exocytosis

Output Details

Genome-wide association studies have identified *Glycoprotein Nmb* (*GPNMB*) as a risk factor for Parkinson’s Disease. The risk allele increases *GPNMB* transcription and GPNMB protein levels in the CSF highlighting GPMNB as a potential biomarker for Parkinson’s Disease. However, a lack of knowledge of GPNMB’s function and mechanism of secretion have hindered an interpretation of secreted GPNMB levels. In this study, we assessed the mechanism of GPNMB secretion by macrophages, the primary cell type expressing GPNMB in the brain. We show that GPNMB is secreted in response to lysosomal stress via lysosomal exocytosis and highlight the Parkinson’s Disease risk factor LRRK2 as a strong modulator of GPNMB secretion.
Tags
  • Cell culture
  • FACS
  • GPNMB
  • Immunofluorescence
  • LRRK2
  • Lysosomal dysfunction
  • Lysosomes
  • Macrophage
  • Microscopy
  • Western Blot

Meet the Authors

  • User avatar fallback logo

    Erin Bogacki, MSc

    Key Personnel: Team Hardy

    Royal Veterinary College

  • User avatar fallback logo

    George Longmore

  • Patrick Lewis, PhD

    Collaborating PI: Team Hardy

    Royal Veterinary College

  • Susanne Herbst, PhD

    Key Personnel: Team Hardy

    Royal Veterinary College