The LINC-anchored actin cap connects the extracellular milieu to the nucleus for ultrafast mechanotransduction

Chambliss, Allison B; Khatau, Shyam B.; Erdenberger, Nicholas; Robinson, D. Kyle; Hodzic, Didier; Longmore, Gregory D.; Wirtz, Denis

doi:10.1038/srep01087

Cited by 170 publications

(175 citation statements)

References 39 publications

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“…In accordance with previous studies (Broers et al, 2004;Khatau et al, 2009Khatau et al, , 2010Kim et al, 2012;Chambliss et al, 2013), the actin cytoskeletal architecture of wild-type MEFs (Lmna +/+ MEFs) and that of MEFs lacking the Lmna gene (Lmna −/− MEFs) showed apparent differences. The majority of Lmna +/+ MEFs (73±5%, mean±s.d.…”

Section: Resultssupporting

confidence: 68%

Cellular strain avoidance is mediated by a functional actin cap – observations in an Lmna-deficient cell model

Tamiello

Halder

Kamps

et al. 2017

Journal of Cell Science

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In adherent cells, the relevance of a physical mechanotransduction pathway provided by the perinuclear actin cap stress fibers has recently emerged. Here, we investigate the impact of a functional actin cap on the cellular adaptive response to topographical cues and uniaxial cyclic strain. Lmna-deficient fibroblasts are used as a model system because they do not develop an intact actin cap, but predominantly form a basal layer of actin stress fibers underneath the nucleus. We observe that topographical cues induce alignment in both normal and Lmna-deficient fibroblasts, suggesting that the topographical signal transmission occurs independently of the integrity of the actin cap. By contrast, in response to cyclic uniaxial strain, Lmna-deficient cells show a compromised strain avoidance response, which is completely abolished when topographical cues and uniaxial strain are applied along the same direction. These findings point to the importance of an intact and functional actin cap in mediating cellular strain avoidance.

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Section: Resultssupporting

confidence: 68%

Cellular strain avoidance is mediated by a functional actin cap – observations in an Lmna-deficient cell model

Tamiello

Halder

Kamps

et al. 2017

Journal of Cell Science

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“…Meanwhile, the nucleoplasmic domains of SUN-domain-containing proteins (yellow) interact with structural components in the nucleoplasm, including lamins, to dissipate forces in the nucleoskeleton (Bone et al, 2014;Haque et al, 2006). Besides their role in nuclear positioning discussed here, LINC complexes also function during homolog pairing in meiosis (Chikashige et al, 2006;Ding et al, 2007;Sato et al, 2009), DNA damage repair (Lei et al, 2012;Lottersberger et al, 2015;Swartz et al, 2014) and mechanotransduction (Chambliss et al, 2013;Lombardi et al, 2011). Thus, LINC complexes are required for a variety of cell and developmental functions, such as those described here.…”

Section: Nuclear Migration In Polarizing Adherent Tissue Culture Cellsmentioning

confidence: 99%

Nuclear migration events throughout development

Bone

Starr

2016

Journal of Cell Science

110

113

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Moving the nucleus to a specific position within the cell is an important event during many cell and developmental processes. Several different molecular mechanisms exist to position nuclei in various cell types. In this Commentary, we review the recent progress made in elucidating mechanisms of nuclear migration in a variety of important developmental models. Genetic approaches to identify mutations that disrupt nuclear migration in yeast, filamentous fungi, Caenorhabditis elegans, Drosophila melanogaster and plants led to the identification of microtubule motors, as well as Sad1p, UNC-84 (SUN) domain and Klarsicht, ANC-1, Syne homology (KASH) domain proteins (LINC complex) that function to connect nuclei to the cytoskeleton. We focus on how these proteins and various mechanisms move nuclei during vertebrate development, including processes related to wound healing of fibroblasts, fertilization, developing myotubes and the developing central nervous system. We also describe how nuclear migration is involved in cells that migrate through constricted spaces. On the basis of these findings, it is becoming increasingly clear that defects in nuclear positioning are associated with human diseases, syndromes and disorders.

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“…[5][6][7][8][9] LINC complexes and nuclear lamins form a solid scaffold for diverse functions including nuclear migration, 10 nuclear shaping and positioning,. 11,12 maintaining the centrosome-nucleus connection, 13,14 mechanotransduction, 15,16 DNA repair, 17,18 nuclear membrane spacing, cancer, and recessive cerebellar ataxia. 25,26,27 However, for several reasons, it is not known how cells regulate these multiple LINC complex functions.…”

Section: Introductionmentioning

confidence: 99%

SUN1 splice variants, SUN1_888, SUN1_785, and predominant SUN1_916, variably function in directional cell migration

Nishioka

Imaizumi

Imada

et al. 2016

Nucleus

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The LINC complex is a multifunctional protein complex that is involved in various processes at the nuclear envelope, such as nuclear migration, mechanotransduction and chromatin tethering in the meiotic phase. However, it remains unknown how these functions are regulated in different cell contexts. An inner nuclear membrane component of the LINC complex, SUN1, is ubiquitously expressed. The human SUN1 gene produces over 10 variants by alternative splicing. Although functions of SUN1 are relatively well characterized, functional differences among SUN1 splice variants are poorly characterized. LINC complex components are associated with a wide range of human diseases; therefore, it is important to understand the functional diversity among SUN1 splice variants. Here, we identified a novel human SUN1 splice variant, SUN1_888. overexpression of the SUN1 splice variants, SUN1_888 or SUN1_785, but not the predominant isoform, SUN1_916, activated directional cell migration. Knockdown of SUN1_888 suppressed cell migration; in contrast depletion of SUN1_916 activated cell migration. In addition, all of investigated SUN1 splicing variants rescued cell migration in SUN1 knock out cell. These results indicate that redundant and non-redundant functions of SUN1 splice variant in directional cell migration and suggest that variable LINC complexes with distinct task may exit. Furthermore, in contrast to previous studies, we showed association between SUN1 and B-type lamins. Interestingly, B-type lamin preferentially interacts with SUN1 but not SUN2. These results suggest that tissue-specific SUN1 variants variably interact with nucleoplasmic partners and allow variable assembly of LINC complexes that can be assigned to distinct tasks.

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The LINC-anchored actin cap connects the extracellular milieu to the nucleus for ultrafast mechanotransduction

Cited by 170 publications

References 39 publications

Cellular strain avoidance is mediated by a functional actin cap – observations in an Lmna-deficient cell model

Cellular strain avoidance is mediated by a functional actin cap – observations in an Lmna-deficient cell model

Nuclear migration events throughout development

SUN1 splice variants, SUN1_888, SUN1_785, and predominant SUN1_916, variably function in directional cell migration

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