A novel protein complex in membrane rafts linking the NR2B glutamate receptor and autophagy is disrupted following traumatic brain injury

Gregory E. Bigford, Ofelia F. Alonso, W. Dalton Dietrich, Robert Keane

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Hyperactivation of N-methyl-d-aspartate receptors (NRs) is associated with neuronal cell death induced by traumatic brain injury (TBI) and many neurodegenerative conditions. NR signaling efficiency is dependent on receptor localization in membrane raft microdomains. Recently, excitotoxicity has been linked to autophagy, but mechanisms governing signal transduction remain unclear. Here we have identified protein interactions between NR2B signaling intermediates and the autophagic protein Beclin-1 in membrane rafts of the normal rat cerebral cortex. Moderate TBI induced rapid recruitment and association of NR2B and pCaMKII to membrane rafts, and translocation of Beclin-1 out of membrane microdomains. Furthermore, TBI caused significant increases in expression of key autophagic proteins and morphological hallmarks of autophagy that were significantly attenuated by treatment with the NR2B antagonist Ro 25-6981. Thus, stimulation of autophagy by NR2B signaling may be regulated by redistribution of Beclin-1 in membrane rafts after TBI.

Original languageEnglish
Pages (from-to)703-720
Number of pages18
JournalJournal of Neurotrauma
Volume26
Issue number5
DOIs
StatePublished - May 1 2009

Fingerprint

Autophagy
Glutamate Receptors
Membrane Microdomains
Membranes
Proteins
Cerebral Cortex
Signal Transduction
Cell Death
Traumatic Brain Injury
Beclin-1

Keywords

  • Autophagy
  • Excitotoxicity
  • Membrane rafts
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

A novel protein complex in membrane rafts linking the NR2B glutamate receptor and autophagy is disrupted following traumatic brain injury. / Bigford, Gregory E.; Alonso, Ofelia F.; Dalton Dietrich, W.; Keane, Robert.

In: Journal of Neurotrauma, Vol. 26, No. 5, 01.05.2009, p. 703-720.

Research output: Contribution to journalArticle

@article{f7aa21a4639344f58d273b65f8f70dbf,
title = "A novel protein complex in membrane rafts linking the NR2B glutamate receptor and autophagy is disrupted following traumatic brain injury",
abstract = "Hyperactivation of N-methyl-d-aspartate receptors (NRs) is associated with neuronal cell death induced by traumatic brain injury (TBI) and many neurodegenerative conditions. NR signaling efficiency is dependent on receptor localization in membrane raft microdomains. Recently, excitotoxicity has been linked to autophagy, but mechanisms governing signal transduction remain unclear. Here we have identified protein interactions between NR2B signaling intermediates and the autophagic protein Beclin-1 in membrane rafts of the normal rat cerebral cortex. Moderate TBI induced rapid recruitment and association of NR2B and pCaMKII to membrane rafts, and translocation of Beclin-1 out of membrane microdomains. Furthermore, TBI caused significant increases in expression of key autophagic proteins and morphological hallmarks of autophagy that were significantly attenuated by treatment with the NR2B antagonist Ro 25-6981. Thus, stimulation of autophagy by NR2B signaling may be regulated by redistribution of Beclin-1 in membrane rafts after TBI.",
keywords = "Autophagy, Excitotoxicity, Membrane rafts, Traumatic brain injury",
author = "Bigford, {Gregory E.} and Alonso, {Ofelia F.} and {Dalton Dietrich}, W. and Robert Keane",
year = "2009",
month = "5",
day = "1",
doi = "10.1089/neu.2008.0783",
language = "English",
volume = "26",
pages = "703--720",
journal = "Journal of Neurotrauma",
issn = "0897-7151",
publisher = "Mary Ann Liebert Inc.",
number = "5",

}

TY - JOUR

T1 - A novel protein complex in membrane rafts linking the NR2B glutamate receptor and autophagy is disrupted following traumatic brain injury

AU - Bigford, Gregory E.

AU - Alonso, Ofelia F.

AU - Dalton Dietrich, W.

AU - Keane, Robert

PY - 2009/5/1

Y1 - 2009/5/1

N2 - Hyperactivation of N-methyl-d-aspartate receptors (NRs) is associated with neuronal cell death induced by traumatic brain injury (TBI) and many neurodegenerative conditions. NR signaling efficiency is dependent on receptor localization in membrane raft microdomains. Recently, excitotoxicity has been linked to autophagy, but mechanisms governing signal transduction remain unclear. Here we have identified protein interactions between NR2B signaling intermediates and the autophagic protein Beclin-1 in membrane rafts of the normal rat cerebral cortex. Moderate TBI induced rapid recruitment and association of NR2B and pCaMKII to membrane rafts, and translocation of Beclin-1 out of membrane microdomains. Furthermore, TBI caused significant increases in expression of key autophagic proteins and morphological hallmarks of autophagy that were significantly attenuated by treatment with the NR2B antagonist Ro 25-6981. Thus, stimulation of autophagy by NR2B signaling may be regulated by redistribution of Beclin-1 in membrane rafts after TBI.

AB - Hyperactivation of N-methyl-d-aspartate receptors (NRs) is associated with neuronal cell death induced by traumatic brain injury (TBI) and many neurodegenerative conditions. NR signaling efficiency is dependent on receptor localization in membrane raft microdomains. Recently, excitotoxicity has been linked to autophagy, but mechanisms governing signal transduction remain unclear. Here we have identified protein interactions between NR2B signaling intermediates and the autophagic protein Beclin-1 in membrane rafts of the normal rat cerebral cortex. Moderate TBI induced rapid recruitment and association of NR2B and pCaMKII to membrane rafts, and translocation of Beclin-1 out of membrane microdomains. Furthermore, TBI caused significant increases in expression of key autophagic proteins and morphological hallmarks of autophagy that were significantly attenuated by treatment with the NR2B antagonist Ro 25-6981. Thus, stimulation of autophagy by NR2B signaling may be regulated by redistribution of Beclin-1 in membrane rafts after TBI.

KW - Autophagy

KW - Excitotoxicity

KW - Membrane rafts

KW - Traumatic brain injury

UR - http://www.scopus.com/inward/record.url?scp=68349151350&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=68349151350&partnerID=8YFLogxK

U2 - 10.1089/neu.2008.0783

DO - 10.1089/neu.2008.0783

M3 - Article

VL - 26

SP - 703

EP - 720

JO - Journal of Neurotrauma

JF - Journal of Neurotrauma

SN - 0897-7151

IS - 5

ER -