PMID- 17151328
OWN - NLM
STAT- MEDLINE
DCOM- 20070314
LR  - 20071115
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 18
IP  - 1
DP  - 2007 Jan
TI  - Expression and targeting of CX3CL1 (fractalkine) in renal tubular epithelial 
      cells.
PG  - 74-83
AB  - The chemokine CX3CL1 plays a key role in glomerulonephritis and can act as both 
      chemoattractant and adhesion molecule. CX3CL1 also is upregulated in 
      tubulointerstitial injury, but little is known about the subcellular distribution 
      and function of CX3CL1 in renal tubular epithelial cells (RTEC). Unexpectedly, it 
      was found that CX3CL1 is expressed predominantly on the apical surface of tubular 
      epithelium in human renal transplant biopsy specimens with acute rejection or 
      acute tubular necrosis. For studying the targeting of CX3CL1 in polarized RTEC, 
      MDCK cells that expressed untagged or green fluorescent protein-tagged CX3CL1 
      were generated. The chemokine was present on the apical membrane and in subapical 
      vesicles. Apical targeting of CX3CL1 was not due to signals that were conferred 
      by its intracellular domain, to associations with lipid rafts, or to 
      O-glycosylation but, rather, depended on N-linked glycosylation of the protein. 
      With the use of fluorescence recovery after photobleaching, it was found that 
      CX3CL1 is immobile in the apical membrane. However, CX3CL1 partitioned with the 
      triton-soluble rather than -insoluble cellular fraction, indicating that it is 
      not associated directly with the actin cytoskeleton or with lipid rafts. 
      Accordingly, disruption of rafts through cholesterol depletion did not render 
      CX3CL1 mobile. For exploration of potential functions of apical CX3CL1, binding 
      of CX3CR1-expressing leukocytes to polarized RTEC was examined. Leukocyte 
      adhesion to the luminal surface was enhanced significantly when CX3CL1 was 
      present. These data demonstrate that CX3CL1 is expressed preferentially on the 
      apical membrane of RTEC and suggest a novel function for the chemokine in 
      recruitment and retention of leukocytes in tubulointerstitial inflammation.
FAU - Durkan, Anne M
AU  - Durkan AM
AD  - Division of Nephrology, Hospital for Sick Children, 555 University Avenue, 
      Toronto, ON, Canada.
FAU - Alexander, R Todd
AU  - Alexander RT
FAU - Liu, Guang-Ying
AU  - Liu GY
FAU - Rui, Min
AU  - Rui M
FAU - Femia, Giuseppe
AU  - Femia G
FAU - Robinson, Lisa A
AU  - Robinson LA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20061206
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (CX3CL1 protein, human)
RN  - 0 (Chemokine CX3CL1)
RN  - 0 (Chemokines, CX3C)
RN  - 0 (DNA Primers)
RN  - 0 (Membrane Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cell Adhesion
MH  - Cell Line
MH  - Cell Membrane/metabolism
MH  - Cell Polarity
MH  - Chemokine CX3CL1
MH  - Chemokines, CX3C/chemistry/*genetics/*metabolism
MH  - DNA Primers/genetics
MH  - Dogs
MH  - Epithelial Cells/cytology/metabolism
MH  - Fluorescence Recovery After Photobleaching
MH  - Gene Expression
MH  - Glycosylation
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Humans
MH  - Kidney Tubules/cytology/*metabolism
MH  - Leukocytes/cytology
MH  - Membrane Proteins/chemistry/*genetics/*metabolism
MH  - Recombinant Fusion Proteins/chemistry/genetics/metabolism
EDAT- 2006/12/08 09:00
MHDA- 2007/03/16 09:00
CRDT- 2006/12/08 09:00
PHST- 2006/12/08 09:00 [pubmed]
PHST- 2007/03/16 09:00 [medline]
PHST- 2006/12/08 09:00 [entrez]
AID - ASN.2006080862 [pii]
AID - 10.1681/ASN.2006080862 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2007 Jan;18(1):74-83. doi: 10.1681/ASN.2006080862. Epub 2006 
      Dec 6.