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Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
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Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

The lysosomal transmembrane protein 9B regulates the activity of inflammatory signaling pathways

Francis Dodeller1, Marie Gottar, Dieter Huesken

  • 1Novartis Institutes for BioMedical Research, Basel, Switzerland.

The Journal of Biological Chemistry
|June 11, 2008
PubMed

Insights

Transmembrane protein 9B (TMEM9B) is a novel regulator of inflammatory signaling. TMEM9B is crucial for producing proinflammatory cytokines via tumor necrosis factor (TNF), interleukin-1beta (IL-1beta), and Toll-like receptor (TLR) pathways.

Area of Science:

  • Cellular Biology
  • Immunology
  • Molecular Signaling

Background:

  • Tumor necrosis factor (TNF) signaling is complex, involving known effectors and potentially novel modulators.
  • Understanding these modulators is key to deciphering TNF's diverse biological actions.

Purpose of the Study:

  • To identify novel regulators of the TNF signaling cascade.
  • To characterize the role of transmembrane protein 9B (TMEM9B) in inflammatory signaling pathways.

Main Methods:

  • Investigated TMEM9B's role in TNF, IL-1beta, and TLR signaling.
  • Assessed TMEM9B's requirement for cytokine production and cell death.
  • Determined TMEM9B's position within the NF-kappaB and MAPK pathways.

Main Results:

  • Identified TMEM9B as a shared component in TNF, IL-1beta, and TLR signaling pathways.
  • TMEM9B expression is essential for proinflammatory cytokine production but not for TNF- or Fas ligand-induced apoptosis.
  • TMEM9B functions upstream of the TAK1 complex, influencing NF-kappaB and MAPK activation.

Conclusions:

  • TMEM9B is a critical regulator of inflammatory signaling pathways.
  • Endosomal and lysosomal compartments play a regulatory role in these inflammatory pathways.

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