PMID- 32210761
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 1662-5099 (Print)
IS  - 1662-5099 (Electronic)
IS  - 1662-5099 (Linking)
VI  - 13
DP  - 2020
TI  - Caspr1 Facilitates sAPPalpha Production by Regulating alpha-Secretase ADAM9 in Brain 
      Endothelial Cells.
PG  - 23
LID - 10.3389/fnmol.2020.00023 [doi]
LID - 23
AB  - The expression of contactin-associated protein 1 (Caspr1) in brain microvascular 
      endothelial cells (BMECs), one of the major cellular components of the 
      neurovascular unit (NVU), has been revealed recently. However, the physiological 
      role of Caspr1 in BMECs remains unclear. We previously reported the 
      nonamyloidogenic processing of amyloid protein precursor (APP) pathway in the 
      human BMECs (HBMECs). In this study, we found Caspr1 depletion reduced the levels 
      of soluble amyloid protein precursor alpha (sAPPalpha) in the supernatant of HBMECs, 
      which could be rescued by expression of full-length Caspr1. Our further results 
      showed that ADAM9, the alpha-secretase essential for processing of APP to generate 
      sAPPalpha, was decreased in Caspr1-depleted HBMECs. The reduced sAPPalpha secretion in 
      Caspr1-depleted HBMECs was recovered by expression of exogenous ADAM9. Then, we 
      identified that Caspr1 specifically regulates the expression of ADAM9, but not 
      ADAM10 and ADAM17, at transcriptional level by nuclear factor-kappaB (NF-kappaB) 
      signaling pathway. Caspr1 knockout attenuated the activation of NF-kappaB and 
      prevented the nuclear translocation of p65 in brain endothelial cells, which was 
      reversed by expression of full-length Caspr1. The reduced sAPPalpha production and 
      ADAM9 expression upon Caspr1 depletion were effectively recovered by NF-kappaB 
      agonist. The results of luciferase assays indicated that the NF-kappaB binding sites 
      are located at -859 bp to -571 bp of ADAM9 promoter. Taken together, our results 
      demonstrated that Caspr1 facilitates sAPPalpha production by transcriptional 
      regulation of alpha-secretase ADAM9 in brain endothelial cells.
CI  - Copyright (c) 2020 Tang, Liu, Li, Wang, Wang, Su, Fang, Qin, Wei, Zhao and Chen.
FAU - Tang, Shi-Yu
AU  - Tang SY
AD  - Department of Developmental Cell Biology, Key Laboratory of Cell Biology, 
      Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry 
      of Education, China Medical University, Shenyang, China.
FAU - Liu, Dong-Xin
AU  - Liu DX
AD  - Department of Developmental Cell Biology, Key Laboratory of Cell Biology, 
      Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry 
      of Education, China Medical University, Shenyang, China.
FAU - Li, Yuan
AU  - Li Y
AD  - Department of Developmental Cell Biology, Key Laboratory of Cell Biology, 
      Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry 
      of Education, China Medical University, Shenyang, China.
FAU - Wang, Kang-Ji
AU  - Wang KJ
AD  - Department of Developmental Cell Biology, Key Laboratory of Cell Biology, 
      Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry 
      of Education, China Medical University, Shenyang, China.
FAU - Wang, Xia-Fei
AU  - Wang XF
AD  - Department of Developmental Cell Biology, Key Laboratory of Cell Biology, 
      Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry 
      of Education, China Medical University, Shenyang, China.
FAU - Su, Zheng-Kang
AU  - Su ZK
AD  - Department of Developmental Cell Biology, Key Laboratory of Cell Biology, 
      Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry 
      of Education, China Medical University, Shenyang, China.
FAU - Fang, Wen-Gang
AU  - Fang WG
AD  - Department of Developmental Cell Biology, Key Laboratory of Cell Biology, 
      Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry 
      of Education, China Medical University, Shenyang, China.
FAU - Qin, Xiao-Xue
AU  - Qin XX
AD  - Department of Developmental Cell Biology, Key Laboratory of Cell Biology, 
      Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry 
      of Education, China Medical University, Shenyang, China.
FAU - Wei, Jia-Yi
AU  - Wei JY
AD  - Department of Developmental Cell Biology, Key Laboratory of Cell Biology, 
      Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry 
      of Education, China Medical University, Shenyang, China.
FAU - Zhao, Wei-Dong
AU  - Zhao WD
AD  - Department of Developmental Cell Biology, Key Laboratory of Cell Biology, 
      Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry 
      of Education, China Medical University, Shenyang, China.
FAU - Chen, Yu-Hua
AU  - Chen YH
AD  - Department of Developmental Cell Biology, Key Laboratory of Cell Biology, 
      Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry 
      of Education, China Medical University, Shenyang, China.
LA  - eng
PT  - Journal Article
DEP - 20200306
PL  - Switzerland
TA  - Front Mol Neurosci
JT  - Frontiers in molecular neuroscience
JID - 101477914
PMC - PMC7068801
OTO - NOTNLM
OT  - ADAM9
OT  - Caspr1
OT  - NF-kappaB
OT  - brain endothelial cells
OT  - sAPPalpha
EDAT- 2020/03/27 06:00
MHDA- 2020/03/27 06:01
PMCR- 2020/01/01
CRDT- 2020/03/27 06:00
PHST- 2019/09/25 00:00 [received]
PHST- 2020/01/31 00:00 [accepted]
PHST- 2020/03/27 06:00 [entrez]
PHST- 2020/03/27 06:00 [pubmed]
PHST- 2020/03/27 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fnmol.2020.00023 [doi]
PST - epublish
SO  - Front Mol Neurosci. 2020 Mar 6;13:23. doi: 10.3389/fnmol.2020.00023. eCollection 
      2020.