Coupling of the nucleus and cytoplasm: Role of the LINC complex

Crisp, Melissa; Liu, Qian; Roux, Kyle J.; Rattner, J. B.; Shanahan, Catherine M.; Burke, Brian; Stahl, Phillip D.; Hodzic, Didier

doi:10.1083/jcb.200509124

Cited by 1,202 publications

(1,521 citation statements)

References 47 publications

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“…Recent biochemical data has demonstrated that SUN-domain proteins are constituents of the inner nuclear membrane and bind KASH-domain proteins (Worman and Gundersen, 2006). SUN-domain proteins are also important for nuclear envelope morphology and link the outer and inner nuclear membranes to the nuclear lamina (Crisp et al, 2006; Figure 2B). …”

Section: Nuclear Envelope Proteinsmentioning

confidence: 99%

Nuclear migration during retinal development

2008

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In this review we focus on the mechanisms, regulation, and cellular consequences of nuclear migration in the developing retina. In the nervous system, nuclear migration is prominent during both proliferative and post-mitotic phases of development. Interkinetic nuclear migration is the process where the nucleus oscillates from the apical to basal surfaces in proliferative neuroepithelia. Proliferative nuclear movement occurs in step with the cell cycle, with M-phase being confined to the apical surface and G1-, S-, and G2-phases occurring at more basal locations. Later, following cell cycle exit, some neuron precursors migrate by nuclear translocation. In this mode of cellular migration, nuclear movement is the driving force for motility. Following discussion of the key components and important regulators for each of these processes, we present an emerging model where interkinetic nuclear migration functions to distinguish cell fates among retinal neuroepithelia. Keywordsinterkinetic nuclear migration; nuclear translocation; nucleokinesis; neurogenesis; dynein; cell cycle; cell behavior OverviewNeuronal development is regulated by a complex array of intrinsic and extrinsic signals that act on progenitor neuroepithelial cells to ensure the correct cell type is generated in the right numbers and at the appropriate time of development (Donovan et al., 2005;Cayouette et al., 2006). In addition, multiple signaling cues are integrated in post-mitotic neuronal precursors to facilitate directed cell migration and correct laminar positioning (Malicki et al., 2004). This spatial and temporal regulation of neuronal cell-type fate commitment and histogenesis is dependent on the regulation of the mitotic cell cycle, and in particular at the level of cell cycle exit (Ohnuma and Harris, 2003). Recent data suggest that nuclear migration is a critical process for several aspects of neuronal development, including that of the neural retina. The focus of this review is on interkinetic nuclear migration and nuclear translocation during retinogenesis, although much of what we know is from observations in other regions of the developing nervous system. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript Interkinetic nuclear migrationInterkinetic nuclear migration is the proliferative cell behavior where the nuclei of neuroepithelial cells migrate in an apical-basal manner and in phase with the cell cycle (Frade 2002). Neuroepithelial cell divisions are confined to apical locations while S-phase occu...

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Section: Nuclear Envelope Proteinsmentioning

confidence: 99%

Nuclear migration during retinal development

2008

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“…Many of these mutations disrupt assembly of the lamins into the lamina. These mutations also affect nuclear morphology and the localization of other proteins in the nuclear envelope, such as emerin or some of the nesprins-large proteins that connect the nuclear lamina to the cellular cytoskeleton via the LINC complex [36].…”

Section: The A-type Laminopathiesmentioning

confidence: 99%

Mouse models of the laminopathies

Stewart

Kozlov

Fong

et al. 2007

Experimental Cell Research

107

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The A and B type lamins are nuclear intermediate filament proteins that comprise the bulk of the nuclear lamina, a thin proteinaceous structure underlying the inner nuclear membrane. The A-type lamins are encoded by the lamin A gene (LMNA). Mutations in this gene have been linked to at least nine diseases, including the progeroid diseases Hutchinson-Gilford progeria and atypical Werner's syndromes, striated muscle diseases including muscular dystrophies and dilated cardiomyopathies, lipodystrophies affecting adipose tissue deposition, diseases affecting skeletal development, and a peripheral neuropathy. To understand how different diseases arise from different mutations in the same gene, mouse lines carrying some of the same mutations found in the human diseases have been established. We, and others have generated mice with different mutations that result in progeria, muscular dystrophy, and dilated cardiomyopathy. To further our understanding of the functions of the lamins, we also created mice lacking lamin B1, as well as mice expressing only one of the Atype lamins. These mouse lines are providing insights into the functions of the lamina and how changes to the lamina affect the mechanical integrity of the nucleus as well as signaling pathways that, when disrupted, may contribute to the disease.

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“…These findings demonstrate that TorA changes the behavior of a subset of LINC complex components, including Sun2 in the INM and nesprin2-Giant and nesprin-3 in the ONM. Indeed, some of the changes in NE membranes caused by redistributed wild-type TorA ( Figure 1BЉ; see also Figure 8A) are reminiscent of changes induced by manipulating components of LINC complexes (Crisp et al, 2006). A recent report of interaction between TorA and nesprin-3 suggests that these effects could be direct (Nery et al, 2008), but further studies are needed to understand the molecular changes involved.…”

Section: Redistributed Tora Displaces a Subset Of Linc Complexmentioning

confidence: 99%

“…SUN proteins participate in NE-spanning LINC complexes (Crisp et al, 2006), which consist of SUN proteins in the inner nuclear membrane (INM) and nesprins in the outer nuclear membrane (ONM; Starr, 2009). Conserved domains of these proteins interact in the perinuclear space to physically connect the nucleus to the cytoskeleton (StewartHutchinson et al, 2008;Starr, 2009).…”

Section: Redistributed Tora Displaces a Subset Of Linc Complexmentioning

confidence: 99%

LULL1 Retargets TorsinA to the Nuclear Envelope Revealing an Activity That Is Impaired by theDYT1Dystonia Mutation

Heyden

Naismith

Snapp

et al. 2009

MBoC

Self Cite

115

162

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TorsinA (TorA) is an AAA؉ ATPase in the endoplasmic reticulum (ER) lumen that is mutated in early onset DYT1 dystonia. TorA is an essential protein in mice and is thought to function in the nuclear envelope (NE) despite localizing throughout the ER. Here, we report that transient interaction of TorA with the ER membrane protein LULL1 targets TorA to the NE. FRAP and Blue Native PAGE indicate that TorA is a stable, slowly diffusing oligomer in either the absence or presence of LULL1. Increasing LULL1 expression redistributes both wild-type and disease-mutant TorA to the NE, while decreasing LULL1 with shRNAs eliminates intrinsic enrichment of disease-mutant TorA in the NE. When concentrated in the NE, TorA displaces the nuclear membrane proteins Sun2, nesprin-2G, and nesprin-3 while leaving nuclear pores and Sun1 unchanged. Wild-type TorA also induces changes in NE membrane structure. Because SUN proteins interact with nesprins to connect nucleus and cytoskeleton, these effects suggest a new role for TorA in modulating complexes that traverse the NE. Importantly, once concentrated in the NE, disease-mutant TorA displaces Sun2 with reduced efficiency and does not change NE membrane structure. Together, our data suggest that LULL1 regulates the distribution and activity of TorA within the ER and NE lumen and reveal functional defects in the mutant protein responsible for DYT1 dystonia.

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Coupling of the nucleus and cytoplasm: Role of the LINC complex

Cited by 1,202 publications

References 47 publications

Nuclear migration during retinal development

Nuclear migration during retinal development

Mouse models of the laminopathies

LULL1 Retargets TorsinA to the Nuclear Envelope Revealing an Activity That Is Impaired by theDYT1Dystonia Mutation

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