PMID- 29358188
OWN - NLM
STAT- MEDLINE
DCOM- 20180919
LR  - 20180919
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 475
IP  - 4
DP  - 2018 Feb 23
TI  - Globular C1q receptor (p33) binds and stabilizes pro-inflammatory MCP-1: a novel 
      mechanism for regulation of MCP-1 production and function.
PG  - 775-786
LID - 10.1042/BCJ20170857 [doi]
AB  - The protein gC1qR (globular C1q receptor), also named p33, was originally 
      identified as a binding partner of the globular heads of C1q in the complement 
      system. gC1qR/p33 is abundantly expressed in many cell types, but the functional 
      importance of this protein is not completely understood. Here, we investigate the 
      impact of gC1qR/p33 on the production and function of the pathophysiologically 
      important chemokine monocyte chemoattractant protein-1 (MCP-1) and the underlying 
      molecular mechanisms. Knockdown of gC1qR/p33 negatively regulated the production 
      of MCP-1, but had no effect on the expression of transcript for MCP-1 in human 
      periodontal ligament cells, suggesting a translational/post-translational 
      mechanism of action. Laser scanning confocal microscopy showed considerable 
      cytosolic co-localization of gC1qR/p33 and MCP-1, and co-immunoprecipitation 
      disclosed direct physical interaction between gC1qR/p33 and MCP-1. Surface 
      plasmon resonance analysis revealed a high-affinity binding (K(D) = 10.9 nM) 
      between gC1qR/p33 and MCP-1. Using a transwell migration assay, we found that 
      recombinant gC1qR/p33 enhances MCP-1-induced migration of human THP-1 monocytes, 
      pointing to a functional importance of the interaction between gC1qR/p33 and 
      MCP-1. An in vitro assay revealed a rapid turnover of the MCP-1 protein and that 
      gC1qR/p33 stabilizes MCP-1, hence preventing its degradation. We propose that 
      endogenous gC1qR/p33 physically interacts with MCP-1 causing stabilization of the 
      MCP-1 protein and stimulation of its activity in human periodontal ligament 
      cells, suggesting a novel gC1qR/p33-mediated pro-inflammatory mechanism of 
      action.
CI  - (c) 2018 The Author(s). Published by Portland Press Limited on behalf of the 
      Biochemical Society.
FAU - Anders, Emma
AU  - Anders E
AD  - Department of Experimental Medical Science, Lund University, BMC D12, Lund 
      SE-22184, Sweden.
FAU - Nebel, Daniel
AU  - Nebel D
AD  - Department of Experimental Medical Science, Lund University, BMC D12, Lund 
      SE-22184, Sweden.
FAU - Westman, Johannes
AU  - Westman J
AD  - Department of Clinical Sciences, Division of Infection Medicine, Lund University, 
      BMC B14, Lund SE-22184, Sweden.
AD  - Program in Cell Biology, The Hospital for Sick Children, 555 University Avenue, 
      Toronto, ON, Canada M5G 1X8.
FAU - Herwald, Heiko
AU  - Herwald H
AD  - Department of Clinical Sciences, Division of Infection Medicine, Lund University, 
      BMC B14, Lund SE-22184, Sweden.
FAU - Nilsson, Bengt-Olof
AU  - Nilsson BO
AUID- ORCID: 0000-0003-2337-8412
AD  - Department of Experimental Medical Science, Lund University, BMC D12, Lund 
      SE-22184, Sweden.
FAU - Svensson, Daniel
AU  - Svensson D
AD  - Department of Experimental Medical Science, Lund University, BMC D12, Lund 
      SE-22184, Sweden daniel.svensson@med.lu.se.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180223
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (C1QBP protein, human)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Mitochondrial Proteins)
SB  - IM
MH  - Carrier Proteins/*genetics/metabolism
MH  - Cell Movement/genetics
MH  - Chemokine CCL2/biosynthesis/chemistry/*genetics
MH  - Cytosol/chemistry/metabolism
MH  - Gene Expression Regulation
MH  - Humans
MH  - Inflammation/*genetics/metabolism/pathology
MH  - Microscopy, Confocal
MH  - Mitochondrial Proteins/*genetics/metabolism
MH  - Monocytes/metabolism/pathology
MH  - Periodontal Ligament/growth & development/*metabolism/pathology
MH  - Protein Binding
MH  - Protein Processing, Post-Translational/genetics
MH  - Surface Plasmon Resonance
OTO - NOTNLM
OT  - MCP-1 (CCL2)
OT  - cytokine
OT  - gC1qR (gC1qBP)
OT  - inflammation
OT  - periodontal ligament cells (PDL cells)
OT  - protein-protein interactions
EDAT- 2018/01/24 06:00
MHDA- 2018/09/20 06:00
CRDT- 2018/01/24 06:00
PHST- 2017/11/09 00:00 [received]
PHST- 2018/01/16 00:00 [revised]
PHST- 2018/01/18 00:00 [accepted]
PHST- 2018/01/24 06:00 [pubmed]
PHST- 2018/09/20 06:00 [medline]
PHST- 2018/01/24 06:00 [entrez]
AID - BCJ20170857 [pii]
AID - 10.1042/BCJ20170857 [doi]
PST - epublish
SO  - Biochem J. 2018 Feb 23;475(4):775-786. doi: 10.1042/BCJ20170857.