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Lymphocyte-Specific Protein 1 Expression in Eukaryotic Cells
Reproduces the Morphologic and Motile Abnormality of NAD 47/89
Neutrophils
Thomas H. Howard,
John Hartwig, and
Casey Cunningham
From the Department of Pediatrics and Cell Biology, University of
Alabama at Birmingham, School of Medicine, Birmingham, AL; and the
Division of Experimental Medicine, Harvard University School of
Medicine, Brigham and Women's Hospital, Boston, MA.
Despite its name, the actin-binding protein
lymphocyte-specific protein1 (LSP1) is found in all hematopoetic cells,
and yet its role in cell function remains unclear. Recently, LSP1 was identified as the 47-kD protein overexpressed in the polymorphonuclear neutrophils of patients with a rare neutrophil disorder, neutrophil actin dysfunction with abnormalities of 47-kD and 89-kD proteins (NAD
47/89). These neutrophils are immotile, defective in actin polymerization in response to agonists, and display distinctive, fine,
"hairlike" F-actin-rich projections on their cell surfaces. We
now show that overexpression of LSP1 produces F-actin bundles that are
likely responsible for the morphologic and motile abnormalities characteristic of the NAD 47/89 phenotype. Coincident with LSP1 overexpression, cells from each of several different eukaryotic lines,
including a highly motile human melanoma line, develop hairlike surface
projections that branch distinctively and contain F-actin and LSP1. The
hairlike projections are supported at their core by thick actin
bundles, composed of actin filaments of mixed polarity, which
periodically anastomose to generate a branching structure. The motility
of the melanoma cells is inhibited even at low levels of LSP1
expression. Therefore, these studies show that overexpression of LSP1
alone can recreate the morphologic and motile defects seen in NAD 47/89
and suggest that LSP1 is distinct from other known actin binding
proteins in its effect on F-actin network structure.
Blood, Vol. 91 No. 12 (June 15), 1998:
pp. 4786-4795
© 1998 by The American Society of Hematology.
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