Activation of Discs large by aPKC aligns the mitotic spindle to the polarity axis during asymmetric cell division
Asymmetric division generates cellular diversity by producing daughter cells with different fates. In animals, the mitotic spindle aligns with Par complex polarized fate determinants, ensuring that fate determinant cortical domains are bisected by the cleavage furrow. Here, we investigate the mechan...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/32137 |
| _version_ | 1811200077466697728 |
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| author | Ognjen Golub Brett Wee Rhonda A Newman Nicole M Paterson Kenneth E Prehoda |
| author_facet | Ognjen Golub Brett Wee Rhonda A Newman Nicole M Paterson Kenneth E Prehoda |
| author_sort | Ognjen Golub |
| collection | DOAJ |
| description | Asymmetric division generates cellular diversity by producing daughter cells with different fates. In animals, the mitotic spindle aligns with Par complex polarized fate determinants, ensuring that fate determinant cortical domains are bisected by the cleavage furrow. Here, we investigate the mechanisms that couple spindle orientation to polarity during asymmetric cell division of Drosophila neuroblasts. We find that the tumor suppressor Discs large (Dlg) links the Par complex component atypical Protein Kinase C (aPKC) to the essential spindle orientation factor GukHolder (GukH). Dlg is autoinhibited by an intramolecular interaction between its SH3 and GK domains, preventing Dlg interaction with GukH at cortical sites lacking aPKC. When co-localized with aPKC, Dlg is phosphorylated in its SH3 domain which disrupts autoinhibition and allows GukH recruitment by the GK domain. Our work establishes a molecular connection between the polarity and spindle orientation machineries during asymmetric cell division. |
| first_indexed | 2024-04-12T01:57:39Z |
| format | Article |
| id | doaj.art-017e4510a527485bb460019b15553120 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:57:39Z |
| publishDate | 2017-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-017e4510a527485bb460019b155531202022-12-22T03:52:45ZengeLife Sciences Publications LtdeLife2050-084X2017-11-01610.7554/eLife.32137Activation of Discs large by aPKC aligns the mitotic spindle to the polarity axis during asymmetric cell divisionOgnjen Golub0Brett Wee1Rhonda A Newman2Nicole M Paterson3Kenneth E Prehoda4https://orcid.org/0000-0003-4214-6158Institute of Molecular Biology, Department of Chemistry and Biochemistry, University of Oregon, Eugene, United StatesInstitute of Molecular Biology, Department of Chemistry and Biochemistry, University of Oregon, Eugene, United StatesInstitute of Molecular Biology, Department of Chemistry and Biochemistry, University of Oregon, Eugene, United StatesInstitute of Molecular Biology, Department of Chemistry and Biochemistry, University of Oregon, Eugene, United StatesInstitute of Molecular Biology, Department of Chemistry and Biochemistry, University of Oregon, Eugene, United StatesAsymmetric division generates cellular diversity by producing daughter cells with different fates. In animals, the mitotic spindle aligns with Par complex polarized fate determinants, ensuring that fate determinant cortical domains are bisected by the cleavage furrow. Here, we investigate the mechanisms that couple spindle orientation to polarity during asymmetric cell division of Drosophila neuroblasts. We find that the tumor suppressor Discs large (Dlg) links the Par complex component atypical Protein Kinase C (aPKC) to the essential spindle orientation factor GukHolder (GukH). Dlg is autoinhibited by an intramolecular interaction between its SH3 and GK domains, preventing Dlg interaction with GukH at cortical sites lacking aPKC. When co-localized with aPKC, Dlg is phosphorylated in its SH3 domain which disrupts autoinhibition and allows GukH recruitment by the GK domain. Our work establishes a molecular connection between the polarity and spindle orientation machineries during asymmetric cell division.https://elifesciences.org/articles/32137cell polarityasymmetric cell divisiontumor suppressorautoinhibitionprotein kinasecell signaling |
| spellingShingle | Ognjen Golub Brett Wee Rhonda A Newman Nicole M Paterson Kenneth E Prehoda Activation of Discs large by aPKC aligns the mitotic spindle to the polarity axis during asymmetric cell division eLife cell polarity asymmetric cell division tumor suppressor autoinhibition protein kinase cell signaling |
| title | Activation of Discs large by aPKC aligns the mitotic spindle to the polarity axis during asymmetric cell division |
| title_full | Activation of Discs large by aPKC aligns the mitotic spindle to the polarity axis during asymmetric cell division |
| title_fullStr | Activation of Discs large by aPKC aligns the mitotic spindle to the polarity axis during asymmetric cell division |
| title_full_unstemmed | Activation of Discs large by aPKC aligns the mitotic spindle to the polarity axis during asymmetric cell division |
| title_short | Activation of Discs large by aPKC aligns the mitotic spindle to the polarity axis during asymmetric cell division |
| title_sort | activation of discs large by apkc aligns the mitotic spindle to the polarity axis during asymmetric cell division |
| topic | cell polarity asymmetric cell division tumor suppressor autoinhibition protein kinase cell signaling |
| url | https://elifesciences.org/articles/32137 |
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