P2RX7-MAPK1/2-SP1 axis inhibits MTOR independent HSPB1-mediated astroglial autophagy

Cell Death & Disease
Ji-Eun KimTae-Cheon Kang

Abstract

Recently, we have reported that heat shock protein B1 (HSPB1) and purinergic receptor P2X7 (P2RX7) are involved in astroglial autophagy (clasmatodendrosis), following status epilepticus (SE). However, the underlying mechanisms of astroglial autophagy have not been completely established. In the present study, we found that the lacking of P2rx7 led to prolonged astroglial HSPB1 induction due to impaired mitogen-activated protein kinase 1/2 (MAPK1/2)-mediated specificity protein 1 (SP1) phosphorylation, following kainic acid-induced SE. Subsequently, the upregulated HSPB1 itself evoked ER stress and exerted protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1, AMPK1)/unc-51 such as autophagy activating kinase 1 (ULK1)- and AKT serine/threonine kinase 1 (AKT1)/glycogen synthase kinase 3 beta (GSK3B)/SH3-domain GRB2-like B1 (SH3GLB1)-mediated autophagic pathways, independent of mechanistic target of rapamycin (MTOR) activity in astrocytes. These findings provide a novel purinergic suppression mechanism to link chaperone expression to autophagy in astrocytes. Therefore, we suggest that P2RX7 may play an important role in the regulation of autophagy by the fine-tuning of HSPB1 expression.

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Citations

Apr 6, 2019·Frontiers in Immunology·Krysta M FelixHsin-Jung Joyce Wu
Feb 6, 2019·Diseases·Janani RameshBhuvarahamurthy Venugopal
Dec 20, 2020·International Journal of Molecular Sciences·Leticia Moreno-GarcíaRosario Osta
Aug 10, 2021·Heliyon·Denis BalabanMatthew Torre

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Methods Mentioned

BETA
protein folding
Protein Assay

Software Mentioned

ImageQuant
AxioVision

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