Nuclear envelope composition determines the ability of neutrophil-type cells to passage through micron-scale constrictions

Citation:

Rowat, A. C. ; Jaalouk, D. E. ; Zwerger, M. ; Ung, L. W. ; Eydelnant, I. A. ; Olins, D. E. ; Olins, A. L. ; Herrmann, H. ; Weitz, D. A. ; Lammerding, J. Nuclear envelope composition determines the ability of neutrophil-type cells to passage through micron-scale constrictions. Journal of Biological Chemistry 2013, 288, 8610-8618. Copy at http://www.tinyurl.com/ma4nryo
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Abstract:

Neutrophils are characterized by their distinct nuclear shape, which is thought to facilitate the transit of these cells through pore spaces less than one-fifth of their diameter. We used human promyelocytic leukemia (HL-60) cells as a model system to investigate the effect of nuclear shape in whole cell deformability. We probed neutrophil-differentiated HL-60 cells lacking expression of lamin B receptor, which fail to develop lobulated nuclei during granulopoiesis and present an in vitro model for Pelger-Huet anomaly; despite the circular morphology of their nuclei, the cells passed through micron-scale constrictions on similar timescales as scrambled controls. We then investigated the unique nuclear envelope composition of neutrophil-differentiated HL-60 cells, which may also impact their deformability; although lamin A is typically down-regulated during granulopoiesis, we genetically modified HL-60 cells to generate a subpopulation of cells with well defined levels of ectopic lamin A. The lamin A-overexpressing neutrophil-type cells showed similar functional characteristics as the mock controls, but they had an impaired ability to pass through micron-scale constrictions. Our results suggest that levels of lamin A have a marked effect on the ability of neutrophils to passage through micron-scale constrictions, whereas the unusual multilobed shape of the neutrophil nucleus is less essential.

Last updated on 07/11/2014