Activation of Discs large by aPKC aligns the mitotic spindle to the polarity axis during asymmetric cell division.

Abstract

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.

• Authors: Ognjen Golub, Brett Wee, Rhonda A Newman, Nicole M Paterson, Kenneth E Prehoda
• Journal: eLife (Elife) Vol. 6 (11 29 2017) ISSN: 2050-084X [Electronic] England
• PMID: 29185419 (Publication Type: Journal Article)

Chemical References

• Drosophila Proteins
• GukH protein, Drosophila
• Nerve Tissue Proteins
• Tumor Suppressor Proteins
• dlg1 protein, Drosophila
• PKC-3 protein
• Protein Kinase C

Topics

• Animals
• Asymmetric Cell Division
• Cells, Cultured
• Drosophila
• Drosophila Proteins (metabolism)
• Nerve Tissue Proteins (metabolism)
• Neurons (physiology)
• Protein Binding
• Protein Kinase C (metabolism)
• Spindle Apparatus (metabolism)
• Tumor Suppressor Proteins (metabolism)