Drosophila Atypical Protein Kinase C Associates with Bazooka and Controls Polarity of Epithelia and Neuroblasts

Abstract

The establishment and maintenance of polarity is of fundamental importance for the function of epithelial and neuronal cells. In Drosophila, the multi-PDZ domain protein Bazooka (Baz) is required for establishment of apico-basal polarity in epithelia and in neuroblasts, the stem cells of the central nervous system. In the latter, Baz anchors Inscuteable in the apical cytocortex, which is essential for asymmetric localization of cell fate determinants and for proper orientation of the mitotic spindle. Here we show that Baz directly binds to the Drosophila atypical isoform of protein kinase C and that both proteins are mutually dependent on each other for correct apical localization. Loss-of-function mutants of the Drosophila atypical isoform of PKC show loss of apico-basal polarity, multilayering of epithelia, mislocalization of Inscuteable and abnormal spindle orientation in neuroblasts. Together, these data provide strong evidence for the existence of an evolutionary conserved mechanism that controls apico-basal polarity in epithelia and neuronal stem cells. This study is the first functional analysis of an atypical protein kinase C isoform using a loss-of-function allele in a genetically tractable organism.

Down-regulated expression of atypical PKC-binding domain deleted asip isoforms in human hepatocellular carcinomas

“…hPar-3 also binds to Par-6 through its first PDZ domain, and this interaction is necessary for tight-junction formation [12]. Another class of proteins that can interact with Asip/Par-3/Bazooka is aPKC [7], [16], [17]. The protein complex including in Cdc42/Rac1, Par-6, Par-3 and aPKC was found to be present under physiological conditions, and this complex may be involved in maintaining the apico-basolateral polarity of epithelia cells [12], [13], [18].…”

Cardiac patterning and morphogenesis in zebrafish

“…Recently, the has locus has been shown to encode an atypical PKC molecule, similar to PKC (Horne-Badovinac et al, 2001;Peterson et al, 2001). In Drosophila, PKC forms a complex with two other proteins (Par-3/Bazooka and Par-6) (Muller and Wieschaus, 1996;Kuchinke et al, 1998;Wodarz et al, 2000;Petronczki and Knoblich, 2001). This complex is found at the apicolateral membrane of epithelial cells, and integrity of the complex is required for the maintenance of epithelial polarity.…”

Isoform‐specific interaction of Flamingo/Starry Night with excess Bazooka affects planar cell polarity in the Drosophila wing

“…Recent data suggest that polarized transport of Fzand Fmi-containing vesicles occurs along polarized microtubule arrays and that their disruption by colchicin interferes with distal localization of prehairs (Shimada et al, 2006). It is tempting to speculate, that bazooka, which is required for spindle orientation in Drosophila neuroblasts Wodarz et al, 1999Wodarz et al, , 2000, provides a link between the cortex and the spindle pole in these cells. Similarly, Bazooka overexpression in wing epithelial cells may affect microtubule orientation and consequently redirect polarized transport of Fmicontaining vesicles.…”

“…In Drosophila and vertebrates, apical-basal polarity of many epithelia is controlled by a group of evolutionarily conserved proteins, Bazooka/Par3, DmPar-6/Par6, and DaPKC/aPKC , which are often associated in a complex localized apical to the zonula adherens (Knust and Bossinger, 2002;Mü ller and Bossinger, 2003;Macara, 2004). In Drosophila, these proteins are essential for the polarization of different cell types, such as epithelial cells, neuroblasts (the precursors of the central nervous system), and oocytes Wodarz et al, 1999Wodarz et al, , 2000Petronczki and Knoblich, 2001;Betschinger et al, 2003;Hutterer et al, 2004). A second evolutionarily conserved protein complex, initially identified in epithelia of Drosophila, comprises the transmembrane protein Crumbs, which is linked by its C-terminal amino acids (ERLI) to the membrane-associated guanylate kinase (MAGUK) Stardust (Bachmann et al, 2001;Hong et al, 2001).…”