| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2039595 | Cell Reports | 2016 | 9 Pages |
•Loss of PDK1 impairs epidermal ACD, differentiation, and stratification•PIP3-PDK1 signaling occurs preferentially at the apical side of dividing basal cells•PDK1 is crucial for activation and recruitment of the apical complex in basal cells•Restoration of Notch rescues the defective differentiation of keratinocytes in vitro
SummaryAsymmetric cell division (ACD) in a perpendicular orientation promotes cell differentiation and organizes the stratified epithelium. However, the upstream cues regulating ACD have not been identified. Here, we report that phosphoinositide-dependent kinase 1 (PDK1) plays a critical role in establishing ACD in the epithelium. Production of phosphatidyl inositol triphosphate (PIP3) is localized to the apical side of basal cells. Asymmetric recruitment of atypical protein kinase C (aPKC) and partitioning defective (PAR) 3 is impaired in PDK1 conditional knockout (CKO) epidermis. PDK1CKO keratinocytes do not undergo calcium-induced activation of aPKC or IGF1-induced activation of AKT and fail to differentiate. PDK1CKO epidermis shows decreased expression of Notch, a downstream effector of ACD, and restoration of Notch rescues defective expression of differentiation-induced Notch targets in vitro. We therefore propose that PDK1 signaling regulates the basal-to-suprabasal switch in developing epidermis by acting as both an activator and organizer of ACD and the Notch-dependent differentiation program.
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