scholarly journals Ensconsin-dependent changes in microtubule organization and LINC complex-dependent changes in nucleus-nucleus interactions result in quantitatively distinct myonuclear positioning defects

2021 ◽  
pp. mbc.E21-06-0324
Author(s):  
Mary Ann Collins ◽  
L. Alexis Coon ◽  
Riya Thomas ◽  
Torrey R. Mandigo ◽  
Elizabeth Wynn ◽  
...  

Nuclear movement is a fundamental process of eukaryotic cell biology. Skeletal muscle presents an intriguing model to study nuclear movement because its development requires the precise positioning of multiple nuclei within a single cytoplasm. Furthermore, there is a high correlation between aberrant nuclear positioning and poor muscle function. Although many genes that regulate nuclear movement have been identified, the mechanisms by which these genes act is not known. Using Drosophila melanogaster muscle development as a model system, and a combination of live-embryo microscopy and laser ablation of nuclei, we have found that clustered nuclei encompass at least two phenotypes that are caused by distinct mechanisms. Specifically, Ensconsin is necessary for productive force production to drive any movement of nuclei whereas Bocksbeutel and Klarsicht are necessary to form distinct populations of nuclei that move to different cellular locations. Mechanisitcally, Ensconsin regulates the number of growing microtubules that are used to move nuclei whereas Bocksbeutel and Klarsicht regulate interactions between nuclei. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text]

2020 ◽  
Author(s):  
Mary Ann Collins ◽  
L. Alexis Coon ◽  
Riya Thomas ◽  
Torrey R. Mandigo ◽  
Elizabeth Wynn ◽  
...  

ABSTRACTNuclear movement is a fundamental process of eukaryotic cell biology. Skeletal muscle presents an intriguing model to study nuclear movement because its development requires the precise positioning of multiple nuclei within a single cytoplasm. Furthermore, there is a high correlation between aberrant nuclear positioning and poor muscle function. Although many genes that regulate nuclear movement have been identified, the mechanisms by which these genes act is not known. Using Drosophila melanogaster muscle development as a model system, and a combination of live-embryo microscopy and laser ablation of nuclei, we have found that phenotypically similar mutants are based in different molecular disruptions. Specifically, ensconsin (Drosophila MAP7) regulates the number of growing microtubules that are used to move nuclei whereas bocksbeutel (Drosophila emerin) and klarsicht (Drosophila KASH-protein regulate interactions between nuclei.


2005 ◽  
Vol 386 (2) ◽  
pp. 201-214 ◽  
Author(s):  
Zhou-shen ZHAO ◽  
Ed MANSER

The Rho GTPases are a family of molecular switches that are critical regulators of signal transduction pathways in eukaryotic cells. They are known principally for their role in regulating the cytoskeleton, and do so by recruiting a variety of downstream effector proteins. Kinases form an important class of Rho effector, and part of the biological complexity brought about by switching on a single GTPase results from downstream phosphorylation cascades. Here we focus on our current understanding of the way in which different Rho-associated serine/threonine kinases, denoted PAK (p21-activated kinase), MLK (mixed-lineage kinase), ROK (Rho-kinase), MRCK (myotonin-related Cdc42-binding kinase), CRIK (citron kinase) and PKN (protein kinase novel), interact with and are regulated by their partner GTPases. All of these kinases have in common an ability to dimerize, and in most cases interact with a variety of other proteins that are important for their function. A diversity of known structures underpin the Rho GTPase–kinase interaction, but only in the case of PAK do we have a good molecular understanding of kinase regulation. The ability of Rho GTPases to co-ordinate spatial and temporal phosphorylation events explains in part their prominent role in eukaryotic cell biology.


Development ◽  
1993 ◽  
Vol 118 (4) ◽  
pp. 1245-1254 ◽  
Author(s):  
W. Sullivan ◽  
P. Fogarty ◽  
W. Theurkauf

Cytoplasmic organization, nuclear migration, and nuclear division in the early syncytial Drosophila embryo are all modulated by the cytoskeleton. In an attempt to identify genes involved in cytoskeletal functions, we have examined a collection of maternal-effect lethal mutations induced by single P-element transposition for those that cause defects in nuclear movement, organization, or morphology during the syncytial embryonic divisions. We describe three mutations, grapes, scrambled, and nuclear-fallout, which define three previously uncharacterized genes. Females homozygous for these mutations produce embryos that exhibit extensive mitotic division errors only after the nuclei migrate to the surface. Analysis of the microfilament and microtubule organization in embryos derived from these newly identified mutations reveal disruptions in the cortical cytoskeleton. Each of the three mutations disrupts the actin-based pseudocleavage furrows and the cellularization furrows in a distinct fashion. In addition to identifying new genes involved in cytoskeletal organization, these mutations provide insights into cytoskeletal function during early Drosophila embryogenesis.


2005 ◽  
Vol 97 (9) ◽  
pp. 743-748 ◽  
Author(s):  
Jean-Claude Mounolou ◽  
François Lacroute

Author(s):  
Soham Ghosh ◽  
Victor Crespo Cuevas ◽  
Benjamin Seelbinder ◽  
Corey P. Neu

ABSTRACTChromatin of the eukaryotic cell nucleus comprises of microscopically dense heterochromatin and loosely packed euchromatin domains, each with distinct transcriptional ability and roles in cellular mechanotransduction. While recent methods have been developed to characterize the nucleus, measurement of intranuclear mechanics remains largely unknown. Here, we describe the development of nuclear elastography, which combines microscopic imaging and computational modeling to quantify the relative elasticity of the heterochromatin and euchromatin domains. Using contracting murine embryonic cardiomyocytes, nuclear elastography reveals that the heterochromatin is almost four times stiffer than the euchromatin at peak deformation. The relative elasticity between the two domains changes rapidly during the active deformation of the cardiomyocyte in the normal physiological condition but progresses more slowly in cells cultured in a mechanically stiff environment, although the relative stiffness at peak deformation does not change. Further, we found that the disruption of the LINC complex in cardiomyocytes compromises the intranuclear elasticity distribution resulting in elastically similar heterochromatin and euchromatin. These results provide insight into the elastography dynamics of heterochromatin and euchromatin domains, and provide a non-invasive framework to further investigate the mechanobiological function of subcellular and subnuclear domains limited only by the spatiotemporal resolution of the image acquisition method.


eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Corentin Claeys Bouuaert ◽  
Karen Lipkow ◽  
Steven S Andrews ◽  
Danxu Liu ◽  
Ronald Chalmers

How do DNA transposons live in harmony with their hosts? Bacteria provide the only documented mechanisms for autoregulation, but these are incompatible with eukaryotic cell biology. Here we show that autoregulation of Hsmar1 operates during assembly of the transpososome and arises from the multimeric state of the transposase, mediated by a competition for binding sites. We explore the dynamics of a genomic invasion using a computer model, supported by in vitro and in vivo experiments, and show that amplification accelerates at first but then achieves a constant rate. The rate is proportional to the genome size and inversely proportional to transposase expression and its affinity for the transposon ends. Mariner transposons may therefore resist post-transcriptional silencing. Because regulation is an emergent property of the reaction it is resistant to selfish exploitation. The behavior of distantly related eukaryotic transposons is consistent with the same mechanism, which may therefore be widely applicable.


2011 ◽  
Vol 32 (4) ◽  
pp. 166
Author(s):  
Sarah E Boyd ◽  
Johnathon M Keith ◽  
Ana Traven ◽  
Traude Beilharz

The foundation for much of our current understanding of eukaryotic cell biology stems from studies exploiting the combined power of this yeast?s genetic tractability and its simple growth requirements. Furthermore, access to an early complete genome in 1996 allowed yeast researchers to spearhead the move toward genome-wide studies that underpin our thinking about systems-level biology today. Indeed, the last decade has been so rich in these studies that it has become close to impossible for most biologists to interrogate the data in an unbiased fashion. The challenge for the next decade is to generate the informational tools to sort the multidimensional datasets for underlying networks.


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