PMID- 30794430
OWN - NLM
STAT- MEDLINE
DCOM- 20200512
LR  - 20200512
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 33
IP  - 5
DP  - 2019 May
TI  - M1 muscarinic receptors regulate the phosphorylation of AMPA receptor subunit 
      GluA1 via a signaling pathway linking cAMP-PKA and PI3K-Akt.
PG  - 6622-6631
LID - 10.1096/fj.201802351R [doi]
AB  - M1 muscarinic acetylcholine receptors are highly expressed in key areas that 
      control cognition, such as the cortex and hippocampus, representing one potential 
      therapeutic target for cognitive dysfunctions of Alzheimer's disease and 
      schizophrenia. We have reported that M1 receptors facilitate cognition by 
      promoting membrane insertion of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic 
      acid receptor AMPA receptor subunit 1 (GluA1) through phosphorylation at Ser845. 
      However, the signaling pathway is still unclear. Here we showed that adenylyl 
      cyclase inhibitor 2',5'-dideoxyadenosine and PKA inhibitor KT5720 inhibited 
      enhancement of phosphorylation of Ser845 and membrane insertion of GluA1 induced 
      by M1 receptor activation. Furthermore, PI3K inhibitor LY294002 and protein 
      kinase B (Akt) inhibitor IV blocked the effects of M1 receptors as well. 
      Remarkably, the increase of the activity of PI3K-Akt signaling induced by M1 
      receptor activation could be abolished by cAMP-PKA inhibitors. Moreover, 
      inhibiting the mammalian target of rapamycin (mTOR) complex 1, an important 
      downstream effector of PI3K-Akt, by short-term application of rapamycin 
      attenuated the effects of M1 receptors on GluA1. Furthermore, such effect was 
      unrelated to possible protein synthesis promoted by mTOR. Taken together, these 
      data demonstrate that M1 receptor activation induces membrane insertion of GluA1 
      via a signaling linking cAMP-PKA and PI3K-Akt-mTOR pathways but is irrelevant to 
      protein synthesis.-Zhao, L.-X., Ge, Y.-H., Li, J.-B., Xiong, C.-H., Law, P.-Y., 
      Xu, J.-R., Qiu, Y., Chen, H.-Z. M1 muscarinic receptors regulate the 
      phosphorylation of AMPA receptor subunit GluA1 via a signaling pathway linking 
      cAMP-PKA and PI3K-Akt.
FAU - Zhao, Lan-Xue
AU  - Zhao LX
AD  - Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Ge, Yan-Hui
AU  - Ge YH
AD  - Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Li, Jia-Bing
AU  - Li JB
AD  - Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Xiong, Cai-Hong
AU  - Xiong CH
AD  - Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Law, Ping-Yee
AU  - Law PY
AD  - Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA; 
      and.
FAU - Xu, Jian-Rong
AU  - Xu JR
AD  - Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Qiu, Yu
AU  - Qiu Y
AD  - Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Chen, Hong-Zhuan
AU  - Chen HZ
AD  - Institute of Interdisciplinary Integrative Biomedical Research, Shanghai 
      University of Traditional Chinese Medicine, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190222
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Receptor, Muscarinic M1)
RN  - 0 (Receptors, AMPA)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - TFZ3H25BS1 (glutamate receptor ionotropic, AMPA 1)
SB  - IM
MH  - Animals
MH  - Cyclic AMP/*metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/*metabolism
MH  - Mechanistic Target of Rapamycin Complex 1/metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Muscarinic M1/*metabolism
MH  - Receptors, AMPA/*metabolism
MH  - Second Messenger Systems/*physiology
OTO - NOTNLM
OT  - GluA1 Ser845
OT  - GluA1 trafficking
OT  - mTOR
OT  - signal transduction
EDAT- 2019/02/23 06:00
MHDA- 2020/05/13 06:00
CRDT- 2019/02/23 06:00
PHST- 2019/02/23 06:00 [pubmed]
PHST- 2020/05/13 06:00 [medline]
PHST- 2019/02/23 06:00 [entrez]
AID - 10.1096/fj.201802351R [doi]
PST - ppublish
SO  - FASEB J. 2019 May;33(5):6622-6631. doi: 10.1096/fj.201802351R. Epub 2019 Feb 22.