Polo inhibits progenitor self-renewal and regulates Numb asymmetry by phosphorylating Pon (Nature, 2007, 449:96-100)

報告日期: 2007/11/09
報告時間: 17:10/18:00
報告學生: 馬志遠
講評老師: 謝清河
附件下載:

Polo inhibits progenitor self-renewal and regulates Numb asymmetry by phosphorylating Pon

Hongyan Wang, Yingshi Ouyang, W. Gregory Somers, William Chia & Bingwei Lu

Nature 449(7158): 96-100

Speaker: Chih-Yuan Ma

Commentator: Prof. Patrick C.H. Hsieh

Time: 17:10~18:00

Room: 602

Abstract:

Asymmetric cell division enables stem cells to maintain cell numbers (self-renewal) and generate differentiated progeny (differentiation). Numb is one factor that is segregated to differentiated daughter cell and inhibits self-renewal during the stem-cell-like neuroblast divisions in Drosophila melanogaster1. Polo is a key regulator of mitosis, meiosis and cytokinesis2. In this study, authors demonstrate Polo directly phosphorylates Partner of Numb (Pon), an adaptor protein for Numb3, and regulates Numb asymmetric localization. In polo mutants, the asymmetric localization of Pon, Numb and atypical protein kinase C are disrupted and mis-segregated to daughter cells, however, other polarity markers are unaffected. Otherwise, the Pon localization domain (Pon-LD) is located at the carboxy terminus of the protein. Authors mutated Pon-LD (S611) to a non-phosphorylatable Ala residue (S611A) and the localization of Pon-LD (S611A) was defective. These evidences suggest that Polo regulates asymmetric localization of Pon and Numb by phosphorylating Pon. The numbers of stem-cell-like neuroblasts were increased in polo mutants, and overexpression of Numb can inhibit this effect. Polo is localized to centrosomes and is required for centrosome organization and separation. When polo was mutated, the tight coupling of spindle was disrupted. These results indicate that Polo controls the self-renewal by regulating the localization and activity of Numb and the orientation of mitotic spindles.

 

References:

1           Lee, C. Y. et al., Drosophila Aurora-A kinase inhibits neuroblast self-renewal by regulating aPKC/Numb cortical polarity and spindle orientation. Genes Dev 20 (24), 3464 (2006).

2           Barr, F. A., Sillje, H. H., and Nigg, E. A., Polo-like kinases and the orchestration of cell division. Nat Rev Mol Cell Biol 5 (6), 429 (2004).

3           Lu, B., Rothenberg, M., Jan, L. Y., and Jan, Y. N., Partner of Numb colocalizes with Numb during mitosis and directs Numb asymmetric localization in Drosophila neural and muscle progenitors. Cell 95 (2), 225 (1998).