PMID- 38352565
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240214
DP  - 2024 Jan 30
TI  - Identifying the function of the NMDA NR1 (C2) subunit through its interaction 
      with Magi-2 during inflammatory pain.
LID - 2024.01.30.578033 [pii]
LID - 10.1101/2024.01.30.578033 [doi]
AB  - Much is understood about the structure and gating properties of NMDA receptors 
      (NMDAR), but the function of the carboxy-terminal splice variant of the NR1 
      subunit, NR1 (C2) has never been identified. By studying the scaffolding protein 
      Magi-2 in animal models of inflammatory pain, we discovered how NR1 (C2) protein 
      is specifically regulated. We found that Magi-2 deficiency resulted in decreased 
      pain behavior and a concomitant reduction in NR1 (C2) protein. Magi-2 contains WW 
      domains, domains typically found in ubiquitin ligases. We identified an atypical 
      WW-binding domain within NR1 (C2) which conferred susceptibility to Nedd4-1 
      ubiquitin-ligase dependent degradation. We used lipidated peptidomimetics derived 
      from the NR1 (C2) sequence and found that NR1 (C2) protein levels and pain 
      behavior can be pharmacologically targeted. The function of NR1 (C2) is to give 
      lability to a pool of NMDAR, important for pain signaling.
FAU - Sheehan, Garrett D
AU  - Sheehan GD
AUID- ORCID: 0000-0003-1508-2304
FAU - Martin, Molly K
AU  - Martin MK
FAU - Roszczyk, Adam
AU  - Roszczyk A
FAU - Hao, Katherient
AU  - Hao K
FAU - Bhattacharjee, Arin
AU  - Bhattacharjee A
AUID- ORCID: 0000-0003-3190-4523
LA  - eng
PT  - Preprint
DEP - 20240130
PL  - United States
TA  - bioRxiv
JT  - bioRxiv : the preprint server for biology
JID - 101680187
PMC - PMC10862890
EDAT- 2024/02/14 06:43
MHDA- 2024/02/14 06:44
PMCR- 2024/02/13
CRDT- 2024/02/14 03:54
PHST- 2024/02/14 06:44 [medline]
PHST- 2024/02/14 06:43 [pubmed]
PHST- 2024/02/14 03:54 [entrez]
PHST- 2024/02/13 00:00 [pmc-release]
AID - 2024.01.30.578033 [pii]
AID - 10.1101/2024.01.30.578033 [doi]
PST - epublish
SO  - bioRxiv [Preprint]. 2024 Jan 30:2024.01.30.578033. doi: 
      10.1101/2024.01.30.578033.