期刊
CELL
卷 128, 期 2, 页码 383-397出版社
CELL PRESS
DOI: 10.1016/j.cell.2006.11.051
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资金
- NIAID NIH HHS [P01 AI053194] Funding Source: Medline
- NIDDK NIH HHS [R01 DK067153] Funding Source: Medline
Formation of the apical surface and lumen is a fundamental, yet poorly understood, step in epithelial organ development. We show that PTEN localizes to the apical plasma membrane during epithelial morphogenesis to mediate the enrichment of Ptdlns(4,5)P-2 at this domain during cyst development in three-dimensional culture. Ectopic Ptdlns(4,5)P-2 at the basolateral surface causes apical proteins to relocalize to the basolateral surface. Annexin 2 (Anx2) binds Ptdlns(4,5)P-2 and is recruited to the apical surface. Anx2 binds Cdc42, recruiting it to the apical surface. Cdc42 recruits aPKC to the apical surface. Loss of function of PTEN, Anx2, Cdc42, or aPKC prevents normal development of the apical surface and lumen. We conclude that the mechanism of PTEN, Ptdlns(4,5)P-2, Anx2, Cdc42, and aPKC controls apical plasma membrane and lumen formation.
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