title: PF-4/CXCL4 and CXCL4L1 exhibit distinct subcellular localization and a differentially regulated mechanism of secretion.
abstract: PF-4/CXCL4 is a member of the CXC chemokine family, which is mainly produced by platelets and known for its pleiotropic biological functions. Recently, the proteic product of a nonallelic variant gene of CXCL4 was isolated from human platelets and named as CXCL4L1. CXCL4L1 shows only 4.3% amino acid divergence in the mature protein, but exhibits a 38% amino acid divergence in the signal peptide region. We hypothesized that this may imply a difference in the cell type in which CXCL4L1 is expressed or a difference in its mode of secretion. In different types of transfected cells, CXCL4 and CXCL4L1 exhibited a distinct subcellular localization and a differential regulation of secretion, CXCL4 being stored in secretory granules and released in response to protein kinase C activation, whereas CXCL4L1 was continuously synthesized and secreted through a constitutive pathway. A protein kinase C-regulated CXCL4 secretion was observed also in lymphocytes, a cell type expressing mainly CXCL4 mRNA, whereas smooth muscle cells, which preferentially expressed CXCL4L1, exhibited a constitutive pathway of secretion. These results demonstrate that CXCL4 and CXCL4L1 exhibit a distinct subcellular localization and are secreted in a differentially regulated manner, suggesting distinct roles in inflammatory or homeostatic processes.
authors.affiliation: Excellence Center for Research, Transfer and High Education De Novo Therapies, University of Florence, Florence, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Lasagni
authors.forename: Renaud
authors.initials: R
authors.lastname: Grepin
authors.forename: Benedetta
authors.initials: B
authors.lastname: Mazzinghi
authors.forename: Elena
authors.initials: E
authors.lastname: Lazzeri
authors.forename: Claudia
authors.initials: C
authors.lastname: Meini
authors.forename: Costanza
authors.initials: C
authors.lastname: Sagrinati
authors.forename: Francesco
authors.initials: F
authors.lastname: Liotta
authors.forename: Francesca
authors.initials: F
authors.lastname: Frosali
authors.forename: Elisa
authors.initials: E
authors.lastname: Ronconi
authors.forename: Nathalie
authors.initials: N
authors.lastname: Alain-Courtois
authors.forename: Lara
authors.initials: L
authors.lastname: Ballerini
authors.forename: Giuseppe Stefano
authors.initials: GS
authors.lastname: Netti
authors.forename: Enrico
authors.initials: E
authors.lastname: Maggi
authors.forename: Francesco
authors.initials: F
authors.lastname: Annunziato
authors.forename: Mario
authors.initials: M
authors.lastname: Serio
authors.forename: Sergio
authors.initials: S
authors.lastname: Romagnani
authors.forename: Andreas
authors.initials: A
authors.lastname: Bikfalvi
authors.forename: Paola
authors.initials: P
authors.lastname: Romagnani
mesh_terms: D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D010978:Platelet Factor 4 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism; D014018:Tissue Distribution; D014162:Transfection
chemical_list: C064936:PF4V1 protein, human; D012333:RNA, Messenger; D010978:Platelet Factor 4