title: Mouse monocyte chemoattractant protein 1 (MCP1) functions as a monomer.
abstract: Monocyte chemoattractant protein 1 (MCP1) is an important chemoattractant for microglia. Rodent MCP1 carries a heavily glycosylated C-terminus, which has been predicted to increase local MCP1 concentration, promote MCP1 dimerization/oligomerization, and facilitate receptor engagement. Previous studies have shown that MCP1 mutant lacking the glycosylated C-terminus cannot dimerize/oligomerize, but has higher chemotactic potency than the wild-type (full-length) MCP1, suggesting that rodent MCP1 may function as a monomer. Although many groups support this hypothesis, there is no direct evidence on whether rodent MCP1 dimer is functional. In this paper, using forced recombinant dimeric MCP1 proteins we show that mouse MCP1 dimer is unable to activate Rac1, promote protrusion of lamellipodia, or induce microglial migration, although it can bind to CCR2 and mediate its internalization. These results support the idea that signaling events mediated by MCP1 require the presence of the monomeric form of this chemokine.
authors.affiliation: Department of Pharmacology, Stony Brook University, Stony Brook, NY 11794-8651, USA. Electronic address: yao.yao@rockefeller.edu.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Pharmacology, Stony Brook University, Stony Brook, NY 11794-8651, USA.
authors.forename: Stella E
authors.initials: SE
authors.lastname: Tsirka
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D015151:Immunoblotting; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D011554:Pseudopodia / Q000187:drug effects; D054390:Receptors, CCR2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054390:Receptors, CCR2; D011994:Recombinant Proteins; D020830:rac1 GTP-Binding Protein
keywords: Chemokine; Dimerization; Migration; Mouse; Recombinant