Abstract:
:Correct spindle orientation is achieved through signaling pathways that provide a molecular link between the cell cortex and spindle microtubules in an F-actin-dependent manner. A conserved cortical protein complex, composed of LGN (also known as GPSM2), NuMA (also known as NUMA1) and dynein-dynactin, plays a key role in establishing proper spindle orientation. It has also been shown that the actin-binding protein MISP and the ERM family, which are activated by lymphocyte-oriented kinase (LOK, also known as STK10) and Ste20-like kinase (SLK) (hereafter, SLK/LOK) in mitosis, regulate spindle orientation. Here, we report that MISP functions downstream of the ERM family member ezrin and upstream of NuMA to allow optimal spindle positioning. We show that MISP directly interacts with ezrin and that SLK/LOK-activated ezrin ensures appropriate cortical MISP levels in mitosis by competing with MISP for actin-binding sites at the cell cortex. Furthermore, we found that regulation of the correct cortical MISP levels, by preventing its excessive accumulation, is essential for crescent-like polarized NuMA localization at the cortex and, as a consequence, leads to highly dynamic astral microtubules. Our results uncover how appropriate MISP levels at the cortex are required for proper NuMA polarization and, therefore, an optimal placement of the mitotic spindle within the cell.This article has an associated First Person interview with the first author of the paper.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Kschonsak YT,Hoffmann Idoi
10.1242/jcs.214544subject
Has Abstractpub_date
2018-05-21 00:00:00issue
10eissn
0021-9533issn
1477-9137pii
jcs.214544journal_volume
131pub_type
杂志文章abstract::The effects of two inhibitors of 3-hydroxy 3-methyl glutaryl-coenzyme A reductase (tunicamycin and mevinolin) on nuclear division in the myxomycete Physarum polycephalum were examined. Tunicamycin exerted a minor effect on division in synchronized cultures, whereas mevinolin delayed the second, third and fourth nuclea...
journal_title:Journal of cell science
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abstract::Alpha4 integrins are used by leukocytes and neural crest derivatives for adhesion and migration during embryogenesis, immune responses and tumour invasion. The pro-migratory activity of alpha4 integrin is mediated in part through the direct binding of the cytoplasmic domain to paxillin. Here, using intermolecular FRET...
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journal_title:Journal of cell science
pub_type: 杂志文章,评审
doi:
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abstract::When expressed in pituitary AtT-20 cells, parotid proline-rich proteins enter the regulated pathway. Because the short N-terminal domain of a basic proline-rich protein is necessary for efficient export from the ER, it has not been possible to evaluate the role of this polypeptide segment as a sorting signal for regul...
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journal_title:Journal of cell science
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更新日期:1994-02-01 00:00:00
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pub_type: 杂志文章
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1988-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1242/jcs.231357
更新日期:2019-10-09 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1242/jcs.138313
更新日期:2013-11-15 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.01333
更新日期:2004-09-15 00:00:00
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pub_type: 杂志文章
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更新日期:2019-02-28 00:00:00
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1994-02-01 00:00:00
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pub_type: 杂志文章
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journal_title:Journal of cell science
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doi:
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:
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pub_type: 杂志文章
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:
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journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1989-07-01 00:00:00
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journal_title:Journal of cell science
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