Nuclear lamins

Abstract

ADLD= : adult-onset autosomal dominant leukodystrophy; CMT= : Charcot-Marie-Tooth; EDMD= : Emery-Dreifuss muscular dystrophy; LAP= : lamin-associated polypeptide; LBR= : lamin B receptor; LGMD1B= : autosomal dominant limb-girdle muscular dystrophy The nuclear envelope is the interface between the nucleus and the rest of the cell and consists of inner and outer nuclear membranes. The nuclear lamina underlies the inner nuclear membrane and is an essential structural element of the nuclear envelope. The nuclear lamina maintains the nuclear architecture and regulates DNA replication and chromatin organization. The major components of the nuclear lamina are the nuclear lamins, including lamin A/C and lamin B. Lamins interact with several other inner nuclear proteins, such as emerin; these interactions are critical for the functional organization of chromatin, transport across the nuclear envelope, and transmission of mechanical signals to the nucleus. Mutations in genes encoding lamins and their associated proteins cause a wide spectrum of diseases called “laminopathies.” Mutations affecting lamin A or associated proteins, such as emerin, produce Emery-Dreifuss muscular dystrophy (EDMD). LMNA mutations also produce autosomal dominant limb-girdle muscular dystrophy (LGMD1B) and Charcot-Marie-Tooth (CMT) disease type 2B1. Duplication in LMNB1 , encoding lamin B1, causes autosomal dominant leukodystrophy. Lamin mutations have also been linked to cardiomyopathy, lipodystrophy, and accelerated aging disorders. The functional organization of the nuclear envelope and the wide spectrum of laminopathies have been the subject of several recent reviews.1,–,7 The principal components of the nuclear envelope are the inner and outer nuclear membranes, separated by the perinuclear space4,8 (figure). The outer nuclear membrane is contiguous with and functionally related …