Phosphoproteomics identifies microglial Siglec‐F inflammatory response during neurodegeneration
Name
msb.20209819.pdf
Description
Published version
Size
3.12 MB
Format
Adobe PDF
Checksum (MD5)
6a813852d428426069c1946bd8c8025f
Author(s)
Morshed, Nader
Ralvenius, William
Nott, Alexander
Watson, Lauren Ashley
Rodriguez, Felicia H
Akay, Leyla Anne
Joughin, Brian Alan
Pao, Ping-Chieh
Penney, Jay
LaRocque, Lauren
Date Issued
December 2020
Journal
Molecular Systems Biology
Publisher
EMBO
Citation
Morshed, Nader et al. "Phosphoproteomics identifies microglial Siglec‐F inflammatory response during neurodegeneration." Molecular Systems Biology 16, 12 (December 2020): e9819 ©2020 The Authors
Version
Final published version
Abstract
Alzheimer’s disease (AD) is characterized by the appearance of amyloid-β plaques, neurofibrillary tangles, and inflammation in brain regions involved in memory. Using mass spectrometry, we have quantified the phosphoproteome of the CK-p25, 5XFAD, and Tau P301S mouse models of neurodegeneration. We identified a shared response involving Siglec-F which was upregulated on a subset of reactive microglia. The human paralog Siglec-8 was also upregulated on microglia in AD. Siglec-F and Siglec-8 were upregulated following microglial activation with interferon gamma (IFNγ) in BV-2 cell line and human stem cell-derived microglia models. Siglec-F overexpression activates an endocytic and pyroptotic inflammatory response in BV-2 cells, dependent on its sialic acid substrates and immunoreceptor tyrosine-based inhibition motif (ITIM) phosphorylation sites. Related human Siglecs induced a similar response in BV-2 cells. Collectively, our results point to an important role for mouse Siglec-F and human Siglec-8 in regulating microglial activation during neurodegeneration.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Picower Institute for Learning and Memory
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.15252/msb.20209819
