HMMR acts in the PLK1-dependent spindle positioning pathway and supports neural development

被引：56

作者：

Connell, Marisa ^{[1
]}

Chen, Helen

Jiang, Jihong ^{[1
]}

Kuan, Chia-Wei ^{[2
]}

Fotovati, Abbas ^{[1
]}

Chu, Tony L. H. ^{[1
]}

He, Zhengcheng ^{[1
]}

Lengyell, Tess C. ^{[3
]}

Li, Huaibiao ^{[4
]}

Kroll, Torsten ^{[4
]}

Li, Amanda M. ^{[1
]}

Goldowitz, Daniel ^{[3
,5
]}

Frappart, Lucien ^{[4
]}

Ploubidou, Aspasia ^{[4
]}

Patel, Milian S. ^{[5
]}

Pilarski, Linda M. ^{[6
]}

Simpson, Elizabeth M. ^{[3
,5
]}

Lange, Philipp F. ^{[7
]}

Allan, Douglas W. ^{[2
,8
]}

Maxwell, Christopher A. ^{[1
,7
]}

机构：

[1] Univ British Columbia, Dept Paediat, Vancouver, BC, Canada

[2] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada

[3] Univ British Columbia, Ctr Mol Med & Therapeut, Vancouver, BC, Canada

[4] Leibniz Inst Aging, Fritz Lipmann Inst, Beutenbergstr, Jena, Germany

[5] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada

[6] Univ Alberta, Dept Oncol, Cross Canc Inst, Edmonton, AB, Canada

[7] BC Childrens Hosp, Michael Cuccione Childhood Canc Res Program, Vancouver, BC, Canada

[8] Univ British Columbia, Life Sci Ctr, Dept Cellular & Physiol Sci, Vancouver, BC, Canada

来源：

ELIFE | 2017年 / 6卷

基金：

加拿大健康研究院;

关键词：

ASYMMETRIC CELL-DIVISION; MEDIATED MOTILITY RHAMM; DYNEIN LIGHT-CHAIN; MITOTIC SPINDLE; CENTROSOME AMPLIFICATION; MICROTUBULE NUCLEATION; MAMMALIAN NEUROGENESIS; PLANAR DIVISIONS; PROTEIN; ORIENTATION;

D O I：

10.7554/eLife.28672

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Oriented cell division is one mechanism progenitor cells use during development and to maintain tissue homeostasis. Common to most cell types is the asymmetric establishment and regulation of cortical NuMA-dynein complexes that position the mitotic spindle. Here, we discover that HMMR acts at centrosomes in a PLK1-dependent pathway that locates active Ran and modulates the cortical localization of NuMA-dynein complexes to correct mispositioned spindles. This pathway was discovered through the creation and analysis of Hmmr-knockout mice, which suffer neonatal lethality with defective neural development and pleiotropic phenotypes in multiple tissues. HMMR over-expression in immortalized cancer cells induces phenotypes consistent with an increase in active Ran including defects in spindle orientation. These data identify an essential role for HMMR in the PLK1-dependent regulatory pathway that orients progenitor cell division and supports neural development.

引用

页数：27

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