Direct association of Bazooka and the Drosophila homolog of the human tumor suppressor PTEN reveals a potential role for phosphoinositides in the control of cell polarity. A. Wodarz , A. Ramrath , W. von Stein , A. Grimm. Inst fuer Genetik, Univ Duesseldorf, Duesseldorf, Germany.

   Bazooka (Baz) is a cytoplasmic protein with three PDZ domains that is required for the establishment of apical-basal polarity of epithelia and neuroblasts. We and others have shown that Baz is localized in the apical cortex of epithelia and neuroblasts and forms a protein complex with an atypical protein kinase C (DaPKC) and with another PDZ protein, PAR-6. In neuroblasts, this apical complex is required for recruitment of Inscuteable, which controls spindle orientation and asymmetric localization of cell fate determinants. In order to identify additional components of the apical complex, we performed a yeast 2-hybrid screen using the PDZ domains of Baz as bait. One interaction partner is the Drosophila homolog of the human tumor suppressor PTEN. PTEN encodes a lipid phosphatase that dephosphorylates phosphatidylinositol(3,4,5)P₃ to generate phosphatidylinositol(4,5)P₂. We have confirmed the association of Baz and PTEN by co-immunoprecipitation and show that Baz and PTEN co-localize in the apical cortex of epithelia and neuroblasts. Furthermore, PTEN mutants show mislocalization of DaPKC and early defects prior to gastrulation, consistent with a role of PTEN in establishment of cell polarity. We propose two functions for PTEN in the apical complex: 1) by dephosphorylation of phosphatidylinositol(3,4,5,)P₃ PTEN may regulate the kinase activity of DaPKC, which is probably activated by the phosphatidylinositol(3,4,5,)P₃-dependent kinase PDK-1. 2) PTEN may affect the organization of the actin cytoskeleton by increasing the local concentration of phosphatidylinositol(4,5)P₂, which acts on several regulators of actin dynamics.