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PMID: 17203073 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

aPKC-mediated phosphorylation regulates asymmetric membrane localization of the cell fate determinant Numb.

The EMBO journal ·Vol. 26 ·No. 2 ·2007-01-24 ·Pages 468-80

Smith CA, Lau KM, Rahmani Z, Dho SE, Brothers G, She YM, Berry DM, Bonneil E, Thibault P, Schweisguth F, Le Borgne R, McGlade CJ

Abstract

In Drosophila, the partition defective (Par) complex containing Par3, Par6 and atypical protein kinase C (aPKC) directs the polarized distribution and unequal segregation of the cell fate determinant Numb during asymmetric cell divisions. Unequal segregation of mammalian Numb has also been observed, but the factors involved are unknown. Here, we identify in vivo phosphorylation sites of mammalian Numb and show that both mammalian and Drosophila Numb interact with, and are substrates for aPKC in vitro. A form of mammalian Numb lacking two protein kinase C (PKC) phosphorylation sites (Numb2A) accumulates at the cell membrane and is refractory to PKC activation. In epithelial cells, mammalian Numb localizes to the basolateral membrane and is excluded from the apical domain, which accumulates aPKC. In contrast, Numb2A is distributed uniformly around the cell cortex. Mutational analysis of conserved aPKC phosphorylation sites in Drosophila Numb suggests that phosphorylation contributes to asymmetric localization of Numb, opposite to aPKC in dividing sensory organ precursor cells. These results suggest a model in which phosphorylation of Numb by aPKC regulates its polarized distribution in epithelial cells as well as during asymmetric cell divisions.

MeSH Terms
Amino Acid Sequence Animals Basement Membrane/metabolism Cell Membrane/metabolism Cell Polarity Cells, Cultured Dogs Drosophila Drosophila Proteins/chemistry,metabolism Epithelial Cells/metabolism,ultrastructure Juvenile Hormones/chemistry,metabolism Molecular Sequence Data Phosphorylation Protein Kinase C/metabolism,physiology Tissue Distribution
Chemicals
Drosophila Proteins Juvenile Hormones numb protein, Drosophila PKC-3 protein Protein Kinase C
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Smith Christian A
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Lau Kimberly M
Rahmani Zohra
Dho Sascha E
Brothers Greg
She Ye Min
Berry Donna M
Bonneil Eric
Thibault Pierre
Schweisguth François
Le Borgne Roland
McGlade C Jane
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7601495
Published
2007-01-24
Epub
2007-00-04
Pages
468-80
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1783459
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7601495 PMC Full Text View journal details
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