Nuclear lamina at the crossroads of the cytoplasm and nucleus

Abstract

The nuclear lamina is a protein meshwork that lines the nuclear envelope in metazoan cells. It is composed largely of a polymeric assembly of lamins, which comprise a distinct sequence homology class of the intermediate filament protein family. On the basis of its structural properties, the lamina originally was proposed to provide scaffolding for the nuclear envelope and to promote anchoring of chromatin and nuclear pore complexes at the nuclear surface. This viewpoint has expanded greatly during the past 25 years, with a host of surprising new insights on lamina structure, molecular composition and functional attributes. It has been established that the self-assembly properties of lamins are very similar to those of cytoplasmic intermediate filament proteins, and that the lamin polymer is physically associated with components of the cytoplasmic cytoskeleton and with a multitude of chromatin and inner nuclear membrane proteins. Cumulative evidence points to an important role for the lamina in regulating signaling and gene activity, and in mechanically coupling the cytoplasmic cytoskeleton to the nucleus. The significance of the lamina has been vaulted to the forefront by the discovery that mutations in lamins and lamina-associated polypeptides lead to an array of human diseases. A key future challenge is to understand how the lamina integrates pathways for mechanics and signaling at the molecular level. Understanding the structure of the lamina from the atomic to supramolecular levels will be essential for achieving this goal.

Defects of Lipid Synthesis Are Linked to the Age-Dependent Demyelination Caused by Lamin B1 Overexpression

“…It not only provides structural integrity to the nucleus but also plays a role in essential cellular processes, such as transcription, DNA replication, DNA repair, and epigenetic regulation (Butin-Israeli et al, 2012;Gerace and Huber, 2012;Jung et al, 2013). There is evidence that genes localized at the nuclear periphery may be subject to transcriptional silencing and lamina associated chromatin is enriched in specific repressive histone marks (Guelen et al, 2008;Stancheva and Schirmer, 2014).…”

“…The A-type lamins, lamins A and C, are alternatively spliced products of the same gene LMNA. Two separate genes, LMNB1 and LMNB2, code for the major B-type lamins (Gerace and Huber, 2012). At least one B-type lamin is thought to be expressed in all somatic cells, whereas lamin A/C is primarily found in differentiated cells (Goldman et al, 2002).…”

“…Two separate genes, LMNB1 and LMNB2, code for the major B-type lamins (Gerace and Huber, 2012). At least one B-type lamin is thought to be expressed in all somatic cells, whereas lamin A/C is primarily found in differentiated cells (Goldman et al, 2002). Although they closely interact to form the nuclear lamina, the A-and B-type lamins are thought to form distinct microdomains and may have independent functions (Shimi et al, 2008).…”

Spatial control of phospholipid flux restricts endoplasmic reticulum sheet formation to allow nuclear envelope breakdown

“…The outer membrane and lumen of the nuclear envelope are directly contiguous with other ER structural elements, whereas passage of proteins to the inner nuclear membrane (INM) is gated by the nuclear pores (Hetzer 2010;English and Voeltz 2013). The chromatin-facing INM is associated with the nuclear lamina, a dense filament meshwork that provides structural support (Hetzer 2010;Gerace and Huber 2012).The ER also serves as a platform for de novo phospholipid synthesis (Fagone and Jackowski 2009;Lagace and Ridgway 2013). A central player is the conserved phosphatase lipin, which converts phosphatidic acid (PA) to diacylglycerol (DAG) Siniossoglou 2013).…”

“…The outer membrane and lumen of the nuclear envelope are directly contiguous with other ER structural elements, whereas passage of proteins to the inner nuclear membrane (INM) is gated by the nuclear pores (Hetzer 2010;English and Voeltz 2013). The chromatin-facing INM is associated with the nuclear lamina, a dense filament meshwork that provides structural support (Hetzer 2010;Gerace and Huber 2012).…”