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The granulocyte nucleus and lamin B receptor: avoiding the ovoid

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Abstract

The major human blood granulocyte, the neutrophil, is an essential component of the innate immunity system, emigrating from blood vessels and migrating through tight tissue spaces to the site of bacterial or fungal infection where they kill and phagocytose invading microbes. Since the late nineteenth century, it has been recognized that the human neutrophil nucleus is distinctly not ovoid as in other cell types, but possesses a lobulated (segmented) shape. This deformable nucleus enhances rapid migration. Recent studies have demonstrated that lamin B receptor (LBR) is necessary for the non-ovoid shape. LBR is an integral membrane protein of the nuclear envelope. A single dominant mutation in humans leads to neutrophils with hypolobulated nuclei (Pelger–Huet anomaly); homozygosity leads to ovoid granulocyte nuclei. Interestingly, LBR is also an enzyme involved in cholesterol metabolism. Homozygosity for null mutations is frequently lethal and associated with severe skeletal deformities. In addition to the necessity for LBR, formation of the mature granulocyte nucleus also depends upon lamin composition and microtubule integrity. These observations are part of a larger question on the relationships between nuclear shape and cellular function.

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Acknowledgment

We dedicate this paper to Prof. H. Stobbe (Charite, Berlin) on the occasion of his 85th birthday. Prof. Stobbe, together with K. Kaps, correctly predicted the increased prevalence of PHA in the village Gelenau from the existence of a single PHA homozygous individual. This facilitated the mapping and identification of the PHA gene in later decades. We would also like to thank L. Shultz (Jackson Laboratory, Bar Harbor, ME, USA), the Max Planck Institute for Molecular Genetics in Berlin, T. Lindner, and H. Herrmann for their ongoing creative and pleasant collaborations. K.H. is a recipient of the Rahel Hirsch scholarship provided by the medical faculty at the Charité Humboldt University, Berlin. K.H. and K.S. are supported by DFG grants SP 144/18 and SFB 577/A9. A.L.O. and D.E.O. wish to thank Bowdoin College for providing laboratory facilities and stimulating colleagues. A.L.O. and D.E.O. are supported by NIH/NHLBI R15 HL075809.

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Authors and Affiliations

  1. Department of Medical Genetics, Charite Humboldt University, Augustenburger Platz 1, 13353, Berlin, Germany

    Katrin Hoffmann & Karl Sperling

  2. Biology Department, Bowdoin College, 6500 College Station, Brunswick, ME, 04011, USA

    Ada L. Olins & Donald E. Olins

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  1. Katrin Hoffmann
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  2. Karl Sperling
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Correspondence to Donald E. Olins.

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Communicated by E.A. Nigg

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Hoffmann, K., Sperling, K., Olins, A.L. et al. The granulocyte nucleus and lamin B receptor: avoiding the ovoid. Chromosoma 116, 227–235 (2007). https://doi.org/10.1007/s00412-007-0094-8

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