PF-4/CXCL4 and CXCL4L1 exhibit distinct subcellular localization and a differentially regulated mechanism of secretion.
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.
Lasagni
Laura
L
Excellence Center for Research, Transfer and High Education De Novo Therapies, University of Florence, Florence, Italy.
Grepin
Renaud
R
Mazzinghi
Benedetta
B
Lazzeri
Elena
E
Meini
Claudia
C
Sagrinati
Costanza
C
Liotta
Francesco
F
Frosali
Francesca
F
Ronconi
Elisa
E
Alain-Courtois
Nathalie
N
Ballerini
Lara
L
Netti
Giuseppe Stefano
GS
Maggi
Enrico
E
Annunziato
Francesco
F
Serio
Mario
M
Romagnani
Sergio
S
Bikfalvi
Andreas
A
Romagnani
Paola
P
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
C064936:PF4V1 protein, human; D012333:RNA, Messenger; D010978:Platelet Factor 4