OBJECTIVE: Lamin B receptor (LBR) is an integral protein of the inner nuclear membrane. Recent studies have demonstrated that genetic deficiency of LBR during granulopoiesis results in hypolobulation of the mature neutrophil nucleus, as observed in human Pelger-Huët anomaly and mouse ichthyosis (ic). In this study, we utilized differentiated early promyelocytes (EPRO cells) that were derived from the bone marrow of homozygous and heterozygous ichthyosis mice to examine changes to the expression of nuclear envelope proteins and heterochromatin structure that result from deficient LBR expression. MATERIALS AND METHODS: Wild-type (+/+), heterozygous (+/ic), and homozygous (ic/ic) granulocytic forms of EPRO cells were analyzed for the expression of multiple lamins and inner nuclear envelope proteins by immunostaining and immunoblotting techniques. The heterochromatin architecture was also examined by immunostaining for histone lysine methylation. RESULTS: Wild-type (+/+) and heterozygous (+/ic) granulocytic forms revealed ring-shaped nuclei and contained LBR within the nuclear envelope; ic/ic granulocytes exhibited smaller ovoid nuclei devoid of LBR. The pericentric heterochromatin of undifferentiated and granulocytic ic/ic cells was condensed into larger spots and shifted away from the nuclear envelope, compared to +/+ and +/ic cell forms. Lamin A/C, which is normally not present in mature granulocytes, was significantly elevated in LBR-deficient EPRO cells. CONCLUSIONS: Our observations suggest roles for LBR during granulopoiesis, which can involve augmenting nuclear membrane growth, facilitating compartmentalization of heterochromatin, and promoting downregulation of lamin A/C expression.
OBJECTIVE:Lamin B receptor (LBR) is an integral protein of the inner nuclear membrane. Recent studies have demonstrated that genetic deficiency of LBR during granulopoiesis results in hypolobulation of the mature neutrophil nucleus, as observed in human Pelger-Huët anomaly and mouseichthyosis (ic). In this study, we utilized differentiated early promyelocytes (EPRO cells) that were derived from the bone marrow of homozygous and heterozygous ichthyosismice to examine changes to the expression of nuclear envelope proteins and heterochromatin structure that result from deficient LBR expression. MATERIALS AND METHODS: Wild-type (+/+), heterozygous (+/ic), and homozygous (ic/ic) granulocytic forms of EPRO cells were analyzed for the expression of multiple lamins and inner nuclear envelope proteins by immunostaining and immunoblotting techniques. The heterochromatin architecture was also examined by immunostaining for histone lysine methylation. RESULTS: Wild-type (+/+) and heterozygous (+/ic) granulocytic forms revealed ring-shaped nuclei and contained LBR within the nuclear envelope; ic/ic granulocytes exhibited smaller ovoid nuclei devoid of LBR. The pericentric heterochromatin of undifferentiated and granulocytic ic/ic cells was condensed into larger spots and shifted away from the nuclear envelope, compared to +/+ and +/ic cell forms. Lamin A/C, which is normally not present in mature granulocytes, was significantly elevated in LBR-deficient EPRO cells. CONCLUSIONS: Our observations suggest roles for LBR during granulopoiesis, which can involve augmenting nuclear membrane growth, facilitating compartmentalization of heterochromatin, and promoting downregulation of lamin A/C expression.
Authors: Katrin Hoffmann; Christine K Dreger; Ada L Olins; Donald E Olins; Leonard D Shultz; Barbara Lucke; Hartmut Karl; Reinhard Kaps; Dietmar Müller; Amparo Vayá; Justo Aznar; Russell E Ware; Norberto Sotelo Cruz; Tom H Lindner; Harald Herrmann; André Reis; Karl Sperling Journal: Nat Genet Date: 2002-07-15 Impact factor: 38.330
Authors: Peter Gaines; Chiung W Tien; Ada L Olins; Donald E Olins; Leonard D Shultz; Lisa Carney; Nancy Berliner Journal: Exp Hematol Date: 2008-06-11 Impact factor: 3.084
Authors: T Haraguchi; T Koujin; T Hayakawa; T Kaneda; C Tsutsumi; N Imamoto; C Akazawa; J Sukegawa; Y Yoneda; Y Hiraoka Journal: J Cell Sci Date: 2000-03 Impact factor: 5.285
Authors: Jae-Won Shin; Kyle R Spinler; Joe Swift; Joel A Chasis; Narla Mohandas; Dennis E Discher Journal: Proc Natl Acad Sci U S A Date: 2013-11-04 Impact factor: 11.205
Authors: Ada L Olins; Markus Langhans; Marc Monestier; Andreas Schlotterer; David G Robinson; Corrado Viotti; Hanswalter Zentgraf; Monika Zwerger; Donald E Olins Journal: Nucleus Date: 2011 Jan-Feb Impact factor: 4.197