Kinase-activity-independent functions of atypical protein kinase C in Drosophila.
Polarity of many cell types is controlled by a protein complex consisting of Bazooka/PAR-3 (Baz), PAR-6 and atypical protein kinase C (aPKC). In Drosophila, the Baz-PAR-6-aPKC complex is required for the control of cell polarity in the follicular epithelium, in ectodermal epithelia and neuroblasts. aPKC is the main signaling component of this complex that functions by phosphorylating downstream targets, while the PDZ domain proteins Baz and PAR-6 control the subcellular localization and kinase activity of aPKC. We compared the mutant phenotypes of an aPKC null allele with those of four novel aPKC alleles harboring point mutations that abolish the kinase activity or the binding of aPKC to PAR-6. We show that these point alleles retain full functionality in the control of follicle cell polarity, but produce strong loss-of-function phenotypes in embryonic epithelia and neuroblasts. Our data, combined with molecular dynamics simulations, show that the kinase activity of aPKC and its ability to bind PAR-6 are only required for a subset of its functions during development, revealing tissue-specific differences in the way that aPKC controls cell polarity.
Department of Stem Cell Biology, DFG Research Center for Molecular Physiology of the Brain, Georg-August-University Göttingen, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany.
Soya
S
Kim
Ieva
I
Gailite
Bernard
B
Moussian
Stefan
S
Luschnig
Maik
M
Goette
Karen
K
Fricke
Mona
M
Honemann-Capito
Helmut
H
Grubmüller
Andreas
A
Wodarz
D000255:Adenosine Triphosphate / Q000378:metabolism; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D016764:Cell Polarity; D002999:Clone Cells; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology / Q000201:enzymology*; D004475:Ectoderm / Q000166:cytology / Q000196:embryology / Q000201:enzymology; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000201:enzymology; D005260:Female; D005854:Germ Cells / Q000166:cytology / Q000201:enzymology; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000201:enzymology; D009865:Oocytes / Q000166:cytology / Q000201:enzymology; D017510:Protein Folding; D011493:Protein Kinase C / Q000378:metabolism*; D021381:Protein Transport
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; C107613:Mira protein, Drosophila; D050505:Mutant Proteins; D000255:Adenosine Triphosphate; C115015:PKC-3 protein; C532584:Par-6 protein, Drosophila; D011493:Protein Kinase C