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Vol. 10, Issue 4, 1163-1178, April 1999
and
*Departments of Cellular and Molecular Pharmacology and of
Persistent directional movement of neutrophils in shallow
chemotactic gradients raises the possibility that cells can increase their sensitivity to the chemotactic signal at the front, relative to
the back. Redistribution of chemoattractant receptors to the anterior
pole of a polarized neutrophil could impose asymmetric sensitivity by
increasing the relative strength of detected signals at the cell's
leading edge. Previous experiments have produced contradictory
observations with respect to receptor location in moving neutrophils.
To visualize a chemoattractant receptor directly during chemotaxis, we
expressed a green fluorescent protein (GFP)-tagged receptor for a
complement component, C5a, in a leukemia cell line, PLB-985.
Differentiated PLB-985 cells, like neutrophils, adhere, spread, and
polarize in response to a uniform concentration of chemoattractant, and
orient and crawl toward a micropipette containing chemoattractant.
Recorded in living cells, fluorescence of the tagged receptor,
C5aR-GFP, shows no apparent increase anywhere on the plasma membrane
of polarized and moving cells, even at the leading edge. During
chemotaxis, however, some cells do exhibit increased amounts of highly
folded plasma membrane at the leading edge, as detected by a
fluorescent probe for membrane lipids; this is accompanied by an
apparent increase of C5aR-GFP fluorescence, which is directly
proportional to the accumulation of plasma membrane. Thus neutrophils
do not actively concentrate chemoattractant receptors at the leading
edge during chemotaxis, although asymmetrical distribution of membrane
may enrich receptor number, relative to adjacent cytoplasmic volume, at
the anterior pole of some polarized cells. This enrichment could help
to maintain persistent migration in a shallow gradient of chemoattractant.
Biochemistry and Biophysics, University of California San
Francisco, San Francisco, California 94143
Online version of this article contains video
material for Figures 1, 2, 4, and 5. Online version available at
www.molbiolcell.org.
Corresponding author. E-mail address:
h_bourne{at}quickmail.ucsf.edu.
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