Orientation of the Mitotic Spindle in the Development of Tubular Organs

Zhong, Tao; Zhou, Jun

doi:10.1002/jcb.25865

Cited by 7 publications

(7 citation statements)

References 34 publications

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“…In addition to CEP170, the most upstream SDA protein, ODF2, is shown to regulate spindle orientation via microtubule organization and stability ( Hung et al, 2016a ). Spindle disorganization has been extensively correlated with cell differentiation, cancer and neurological diseases such as microcephaly and lissencephaly ( Noatynska et al, 2012 ), as well as with tubular organ diseases ( Zhong and Zhou, 2017 ). Whether α- and γ-taxilin are involved in development and diseases needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

α-/γ-Taxilin are required for centriolar subdistal appendage assembly and microtubule organization

Wang

et al. 2022

eLife

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The centrosome composed of a pair of centrioles (mother and daughter) and pericentriolar material, and is mainly responsible for microtubule nucleation and anchorage in animal cells. The subdistal appendage (SDA) is a centriolar structure located at the mother centriole’s subdistal region, and it functions in microtubule anchorage. However, the molecular composition and detailed structure of the SDA remain largely unknown. Here, we identified α-taxilin and γ-taxilin as new SDA components that form a complex via their coiled-coil domains and that serve as a new subgroup during SDA hierarchical assembly. The taxilins’ SDA localization is dependent on ODF2, and α-taxilin recruits CEP170 to the SDA. Functional analyses suggest that α- and γ-taxilin are responsible for SDA structural integrity and centrosomal microtubule anchorage during interphase and for proper spindle orientation during metaphase. Our results shed light on the molecular components and functional understanding of the SDA hierarchical assembly and microtubule organization.

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Section: Discussionmentioning

confidence: 99%

α-/γ-Taxilin are required for centriolar subdistal appendage assembly and microtubule organization

Wang

et al. 2022

eLife

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“…In addition to CEP170, the most upstream SDA protein, ODF2, was shown to regulate spindle orientation via microtubule organization and stability (Hung et al, 2016a). Spindle misorganization has been extensively correlated with cell differentiation, cancer and neurological diseases such as microcephaly and lissencephaly (Noatynska et al, 2012), as well as tubular organ diseases (Zhong and Zhou, 2017). Whether α-and γ-taxilin are involved in development and diseases needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

α-/γ-Taxilin are required for centriolar subdistal appendage assembly and microtubule organization

Wang

et al. 2021

Preprint

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The centrosome, composed of a pair of centrioles (mother and daughter centrioles) and pericentriolar material, is mainly responsible for microtubule nucleation and anchorage in animal cells. The subdistal appendage (SDA) is a centriolar structure located at the subdistal region on the mother centriole, and it functions in microtubule anchorage. However, the molecular composition and detailed structure of SDA remain largely unknown. Here, we identified a-taxilin and r-taxilin as new SDA components, which form a complex via their coiled-coil domains and serve as a new subgroup during SDA hierarchical assembly. Their SDA localization is dependent on ODF2, and α-Taxilin recruits CEP170 to the SDA. Functional analyses suggest that α-taxilin and γ-taxilin are responsible for centrosomal microtubule anchorage during interphase, as well as for proper spindle orientation during metaphase. Altogether, our results shed light on the molecular components and functional understanding of the SDA hierarchical assembly and microtubule organization.

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“…Spindle misorientation caused by dysfunction or perturbations in the regulatory mechanisms of spindle orientation is observed in both polarized and nonpolarized cells 2–8 . Increasing evidence indicates that inadequate regulation of spindle orientation contributes to diseases, such as cancer and unfavorable tissue conditions, such as skin aging 9–12 . The development of novel pharmacological approaches to correct spindle misorientation could help to prevent or treat cancer or improve skin conditions.…”

Section: Introductionmentioning

confidence: 99%

2‐O‐Octadecylascorbic acid represses RhoGDIβ expression and ameliorates DNA damage‐induced abnormal spindle orientations

Doi

Togari

Minagi

et al. 2021

J of Cellular Biochemistry

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The appropriate regulation of spindle orientation maintains proper tissue homeostasis and avoids aberrant tissue repair or regeneration. Spindle misorientation due to imbalance or improper functioning leads to a loss of tissue integrity and aberrant growth, such as tissue loss or overgrowth. Pharmacological manipulation to prevent spindle misorientation will enable a better understanding of how spindle orientation is involved in physiological and pathological conditions and will provide therapeutic possibilities to treat patients associated with abnormal tissue function caused by spindle misorientation. N‐terminal‐deleted Rho guanine nucleotide dissociation inhibitor β (RhoGDIβ/RhoGDI2/LyGDI) produced by caspase‐3 activation perturbs spindle orientation in surviving cells following exposure to either ionizing radiation or UVC. Thus, presumably, RhoGDIβ cleaved by caspase‐3 activation acts as a determinant of radiation‐induced spindle misorientation that promote aberrant tissue repair due to deregulation of directional organization of cell population and therefore becomes a potential target of drugs to prevent such response. The objective of this study was to screen and identify chemicals that suppress RhoGDIβ expression. We focused our attention on ascorbic acid (AA) derivatives because of their impact on the maintenance of skin tissue homeostasis. Here, we screened for AA derivatives that suppress RhoGDIβ expression in HeLa cells and identified a lipophilic derivative, 2‐O‐octadecylascorbic acid (2‐OctadecylAA), as a novel RhoGDIβ inhibitor that ameliorated ionizing radiation‐induced abnormal spindle orientations. Among all examined AA derivatives, which were also antioxidative, the inhibition activity was specific to 2‐OctadecylAA. Therefore, this activity was not due to simple antioxidant properties. 2‐OctadecylAA was previously shown to prevent hepatocellular carcinoma development. Our findings suggest that the anticarcinogenic effects of 2‐OctadecylAA are partly due to RhoGDIβ inhibition mechanisms by which spindle orientation perturbations are attenuated. Thus, the molecular targeting features of RhoGDIβ warrant its further development for the treatment or control of spindle orientation abnormalities that affect epithelial homeostasis.

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Orientation of the Mitotic Spindle in the Development of Tubular Organs

Cited by 7 publications

References 34 publications

α-/γ-Taxilin are required for centriolar subdistal appendage assembly and microtubule organization

α-/γ-Taxilin are required for centriolar subdistal appendage assembly and microtubule organization

α-/γ-Taxilin are required for centriolar subdistal appendage assembly and microtubule organization

2‐O‐Octadecylascorbic acid represses RhoGDIβ expression and ameliorates DNA damage‐induced abnormal spindle orientations

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