scholarly journals Dynamic localization of C. elegans TPR-GoLoco proteins mediates mitotic spindle orientation by extrinsic signaling

Development ◽  
2011 ◽  
Vol 138 (20) ◽  
pp. 4411-4422 ◽  
Author(s):  
A. D. Werts ◽  
M. Roh-Johnson ◽  
B. Goldstein
Keyword(s):  
Mitotic Spindle ◽  
Spindle Orientation ◽  
Dynamic Localization ◽  
C Elegans

scholarly journals Mitotic control of kinetochore-associated dynein and spindle orientation by human Spindly

2009 ◽  
Vol 185 (5) ◽  
pp. 859-874 ◽  
Author(s):  
Ying Wai Chan ◽  
Luca L. Fava ◽  
Andreas Uldschmid ◽  
Michael H.A. Schmitz ◽  
Daniel W. Gerlich ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Critical Role ◽  
Spindle Orientation ◽  
Aurora B ◽  
C Elegans ◽  
Spindle Rotation ◽  
Mitotic Control ◽  
New Protein

Mitotic spindle formation and chromosome segregation depend critically on kinetochore–microtubule (KT–MT) interactions. A new protein, termed Spindly in Drosophila and SPDL-1 in C. elegans, was recently shown to regulate KT localization of dynein, but depletion phenotypes revealed striking differences, suggesting evolutionarily diverse roles of mitotic dynein. By characterizing the function of Spindly in human cells, we identify specific functions for KT dynein. We show that localization of human Spindly (hSpindly) to KTs is controlled by the Rod/Zw10/Zwilch (RZZ) complex and Aurora B. hSpindly depletion results in reduced inter-KT tension, unstable KT fibers, an extensive prometaphase delay, and severe chromosome misalignment. Moreover, depletion of hSpindly induces a striking spindle rotation, which can be rescued by co-depletion of dynein. However, in contrast to Drosophila, hSpindly depletion does not abolish the removal of MAD2 and ZW10 from KTs. Collectively, our data reveal hSpindly-mediated dynein functions and highlight a critical role of KT dynein in spindle orientation.

scholarly journals Interaction between Discs large and Pins/LGN/GPSM2: A comparison across species

Biology Open ◽  
2021 ◽  
Author(s):  
Emily A. Schiller ◽  
Dan T. Bergstralh
Keyword(s):  
Cell Fate ◽  
Mitotic Spindle ◽  
Evolutionary History ◽  
Scaffolding Protein ◽  
Spindle Orientation ◽  
C Elegans ◽  
Discs Large ◽  
Canonical Pathways ◽  
History Of ◽  
Multicellular Organisms

The orientation of the mitotic spindle determines the direction of cell division, and therefore contributes to tissue shape and cell fate. Interaction between the multifunctional scaffolding protein Discs large (Dlg) and the canonical spindle orienting factor GPSM2 (called Pins in Drosophila and LGN in vertebrates) has been established in bilaterian models, but its function remains unclear. We used a phylogenetic approach to test whether the interaction is obligate in animals, and in particular whether Pins/LGN/GPSM2 evolved in multicellular organisms as a Dlg-binding protein. We show that Dlg diverged in C. elegans and the syncytial sponge O. minuta and propose that this divergence may correspond to differences in spindle orientation requirements between these organisms and the canonical pathways described in bilaterians. We also demonstrate that Pins/LGN/GPSM2 is present in basal animals, but the established Dlg-interaction site cannot be found in either Placozoa or Porifera. Our results suggest that the interaction between Pins/LGN/GPSM2 and Dlg appeared in Cnidaria, and we therefore speculate that it may have evolved to promote accurate division orientation in the nervous system. This work reveals the evolutionary history of the Pins/LGN/GPSM2-Dlg interaction and suggests new possibilities for its importance in spindle orientation during epithelial and neural tissue development.

scholarly journals Interaction between Discs large and GPSM2: A Comparison Across Species

2021 ◽  
Author(s):  
Emily Schiller ◽  
Dan T Bergstralh
Keyword(s):  
Cell Fate ◽  
Mitotic Spindle ◽  
Evolutionary History ◽  
Scaffolding Protein ◽  
Spindle Orientation ◽  
C Elegans ◽  
Discs Large ◽  
Canonical Pathways ◽  
History Of ◽  
Multicellular Organisms

The orientation of the mitotic spindle determines the direction of cell division, and therefore contributes to tissue shape and cell fate. Interaction between the multifunctional scaffolding protein Discs large (Dlg) and the canonical spindle orienting factor GPSM2 (also called Pins in Drosophila and LGN in vertebrates) has been established in bilaterian models, but its function remains unclear. We used a phylogenetic approach to test whether the interaction is obligate in animals, and in particular whether GPSM2 evolved in multicellular organisms as a Dlg-binding protein. We show that Dlg diverged in C. elegans and the syncytial sponge O. minuta and propose that this divergence may correspond to differences in spindle orientation requirements between these organisms and the canonical pathways described in bilaterians. We also demonstrate that GPSM2 is present in basal animals, but the established Dlg-interaction site cannot be found in either Placozoa or Porifera. Our results suggest that the interaction between GPSM2 and Dlg appeared in Cnidaria, and we therefore speculate that it may have evolved to promote accurate division orientation in the nervous system. This work reveals the evolutionary history of the GPSM2/Dlg interaction and suggests new possibilities for its importance in spindle orientation during epithelial and neural tissue development.

scholarly journals Loss of MYO5B expression deregulates late endosome size which hinders mitotic spindle orientation

PLoS Biology ◽  
2019 ◽  
Vol 17 (11) ◽  
pp. e3000531 ◽  
Author(s):  
Changsen Leng ◽  
Arend W. Overeem ◽  
Fernando Cartón-Garcia ◽  
Qinghong Li ◽  
Karin Klappe ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Late Endosome ◽  
Spindle Orientation

scholarly journals NuMA-microtubule interactions are critical for spindle orientation and the morphogenesis of diverse epidermal structures

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Lindsey Seldin ◽  
Andrew Muroyama ◽  
Terry Lechler
Keyword(s):  
Cell Fate ◽  
Mitotic Spindle ◽  
Cell Types ◽  
Epidermal Differentiation ◽  
Spindle Orientation ◽  
Direct Function ◽  
Spindle Positioning ◽  
Adult Mice ◽  
Neonatal Lethality ◽  
The Matrix

Mitotic spindle orientation is used to generate cell fate diversity and drive proper tissue morphogenesis. A complex of NuMA and dynein/dynactin is required for robust spindle orientation in a number of cell types. Previous research proposed that cortical dynein/dynactin was sufficient to generate forces on astral microtubules (MTs) to orient the spindle, with NuMA acting as a passive tether. In this study, we demonstrate that dynein/dynactin is insufficient for spindle orientation establishment in keratinocytes and that NuMA’s MT-binding domain, which targets MT tips, is also required. Loss of NuMA-MT interactions in skin caused defects in spindle orientation and epidermal differentiation, leading to neonatal lethality. In addition, we show that NuMA-MT interactions are also required in adult mice for hair follicle morphogenesis and spindle orientation within the transit-amplifying cells of the matrix. Loss of spindle orientation in matrix cells results in defective differentiation of matrix-derived lineages. Our results reveal an additional and direct function of NuMA during mitotic spindle positioning, as well as a reiterative use of spindle orientation in the skin to build diverse structures.

scholarly journals Warts Phosphorylates Mud to Promote Pins-Mediated Mitotic Spindle Orientation in Drosophila , Independent of Yorkie

2015 ◽  
Vol 25 (21) ◽  
pp. 2751-2762 ◽  
Author(s):  
Evan B. Dewey ◽  
Desiree Sanchez ◽  
Christopher A. Johnston
Keyword(s):  
Mitotic Spindle ◽  
Spindle Orientation

scholarly journals PTEN controls glandular morphogenesis through a juxtamembrane β-Arrestin1/ARHGAP21 scaffolding complex

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Arman Javadi ◽  
Ravi K Deevi ◽  
Emma Evergren ◽  
Elodie Blondel-Tepaz ◽  
George S Baillie ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Molecular Mechanisms ◽  
Regulatory Protein ◽  
Membrane Binding ◽  
Three Dimensional ◽  
Spindle Orientation ◽  
C2 Domain ◽  
Gtpase Activating Protein ◽  
Defective Mutant ◽  
Glandular Morphogenesis

PTEN controls three-dimensional (3D) glandular morphogenesis by coupling juxtamembrane signaling to mitotic spindle machinery. While molecular mechanisms remain unclear, PTEN interacts through its C2 membrane-binding domain with the scaffold protein β-Arrestin1. Because β-Arrestin1 binds and suppresses the Cdc42 GTPase-activating protein ARHGAP21, we hypothesize that PTEN controls Cdc42 -dependent morphogenic processes through a β-Arrestin1-ARHGAP21 complex. Here, we show that PTEN knockdown (KD) impairs β-Arrestin1 membrane localization, β-Arrestin1-ARHGAP21 interactions, Cdc42 activation, mitotic spindle orientation and 3D glandular morphogenesis. Effects of PTEN deficiency were phenocopied by β-Arrestin1 KD or inhibition of β-Arrestin1-ARHGAP21 interactions. Conversely, silencing of ARHGAP21 enhanced Cdc42 activation and rescued aberrant morphogenic processes of PTEN-deficient cultures. Expression of the PTEN C2 domain mimicked effects of full-length PTEN but a membrane-binding defective mutant of the C2 domain abrogated these properties. Our results show that PTEN controls multicellular assembly through a membrane-associated regulatory protein complex composed of β-Arrestin1, ARHGAP21 and Cdc42.

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