When Lamins Go Bad: Nuclear Structure and Disease

Abstract

When mutations in nuclear lamins were first identified in skeletal and cardiac muscle diseases, the molecular events underlying pathogenesis were mere points of speculation. As more and more unrelated diseases were linked to lamins and other nuclear envelope proteins, nuclear structure and disease became an increasingly prominent research focus. Today, the disease mechanisms remain unresolved, but incredible progress has occurred. Nuclear envelope dysfunction is not only associated with altered nuclear activity, but also impaired structural dynamics and aberrant cell signaling. Building on these findings, small molecules are being discovered in animal models that may become effective therapeutic agents.

Homozygous Pelger-Huet anomaly in three different crossbred rabbits: a case report

“…This receptor is an inner nuclear membrane protein that interacts with heterochromatin, and thus is responsible for the maturation of neutrophil granulocytes (Cohen et al 2007;Hoffmann et al 2007). It is presumed that its disruption causes abnormalities in nuclear heterochromatin morphology (Vale et al 2011), result- ing in altered nuclear activity, impaired structural dynamics, and aberrant cell signalling (Schreiber and Kennedy 2013). The expression of the lamin B receptor in lymphoblastoid cells is reduced in heterozygous cases and is very low in homozygous cases of PHA as compared to normal lymphoblastoid cells (Hoffmann et al 2002).…”

MicroRNAs in hereditary and sporadic premature aging syndromes and other laminopathies

“…Hereditary laminopathies are therefore caused by mutations in genes encoding lamins (primary forms) or proteins implicated in their maturation, such as ZMPSTE24, and in genes encoding their partners (secondary forms; Schreiber & Kennedy, 2013; Worman, 2012; Worman & Bonne, 2007). Laminopathies can also be acquired.…”

Trapping cells in senescence with a lamin cage

“…The importance of an optimal cytoplasmic-nuclear barrier is well illustrated by the fact that mutations in lamin A-a structural component of the nuclear lamina-can cause accelerated aging disorders such as the HutchinsonGilford (HG) progeria syndrome. 2 The presence of a physical barrier between the genome and the cytoplasm raises a major regulatory challenge during cell division. Indeed, to effectively segregate their genome, mitotic cells must attach chromosomes on microtubules emanating from a cytoplasmic structure, the centrosome.…”