LMNB2

LMNB2 Background

The human gene LMNB2 encodes nuclear lamin B2, an intermediate filament protein of the nuclear envelope ^[1]. LMNB2 binding to the nuclear envelope is mediated by a specific binding partner, the lamin B receptor (LBR). LMNB2 shares about 60% of amino acid sequences identical to LMNB1 ^[2]. LMNB1 and LMNB2 are each expressed at the highest levels in different neuronal cell types, suggesting both overlapping and potentially unique roles during brain development ^[3]. This finding is further demonstrated by John M Lee and coworkers. They discovered that both Lmnb1–/– and Lmnb2–/–mice manifested neurodevelopmental abnormalities similar to those in conventional knockout mice, indicating that LMNB1 and LMNB2 have unique functions and that increased production of one B-type lamin cannot compensate for the loss of the other ^[4]. A recent study has shown that LMNB2-null mice have grossly abnormal development of the cerebral cortex and cerebellum ^[5]. This phenotype, known as lissencephaly, is due to defective migration of nuclei within developing LMNB2-deficient mouse neurons. Thus, LMNB2 is a crucial nucleoskeletal component of the nuclear migration machinery in mammals, along with the NE-spanning LINC complexes formed by SUN-domain proteins and Syne/Nesprin proteins ^[6][7]. In addition to the roles in neurons, LMNB2 can also modulate the morphology, dynamics, and function of the nucleolus ^[8].

[1] Biamonti G, Giacca M, et al. The gene for a novel human lamin maps at a highly transcribed locus of chromosome 19 which replicates at the onset of S-phase. Mol Cell Biol. 1992 Aug; 12(8):3499-506.
[2] Davies BSJ, Coffinier C, et al. Posttranslational Processing of Nuclear Lamins. The Enzymes. 2011;29:21-41.
[3] Takamori Y, Tamura Y, et al. Differential expression of nuclear lamin, the major component of nuclear lamina, during neurogenesis in two germinal regions of adult rat brain. Eur J Neurosci. 2007 Mar; 25(6):1653-62.
[4] John M Lee, Hea-Jin Jung, et al. Do lamin B1 and lamin B2 have redundant functions [J]? Nucleus. 2014 Jul 1; 5(4): 287-292.
[5] Coffinier C, Chang SY, et al. Abnormal development of the cerebral cortex and cerebellum in the setting of lamin B2 deficiency. Proc Natl Acad Sci U S A. 2010 Mar 16; 107(11):5076-81.
[6] Zhang X, Lei K, et al. SUN1/2 and Syne/Nesprin-1/2 complexes connect centrosome to the nucleus during neurogenesis and neuronal migration in mice. Neuron. 2009 Oct 29; 64(2):173-87.
[7] Burke B, Roux KJ. Nuclei take a position: managing nuclear location. Dev Cell. 2009 Nov; 17(5):587-97.
[8] Ayantika Sen Gupta, Kundan Sengupta. Lamin B2 Modulates Nucleolar Morphology, Dynamics, and Function [J]. Molecular and Cellular Biology Nov 2017, 37 (24) e00274-17.