PKCgamma regulates syndecan-2 inside-out signaling during xenopus left-right development.
The transmembrane proteoglycan syndecan-2 cell nonautonomously regulates left-right (LR) development in migrating mesoderm by an unknown mechanism, leading to LR asymmetric gene expression and LR orientation of the heart and gut. Here, we demonstrate that protein kinase C gamma (PKCgamma) mediates phosphorylation of the cytoplasmic domain of syndecan-2 in right, but not left, animal cap ectodermal cells. Notably, both phosphorylation states of syndecan-2 are obligatory for normal LR development, with PKCgamma-dependent phosphorylated syndecan-2 in right ectodermal cells and nonphosphorylated syndecan-2 in left cells. The ectodermal cells contact migrating mesodermal cells during early gastrulation, concurrent with the transmission of LR information. This precedes the appearance of monocilia and is one of the earliest steps of LR development. These results demonstrate that PKCgamma regulates the cytoplasmic phosphorylation of syndecan-2 and, consequently, syndecan-2-mediated inside-out signaling to adjacent cells.
Kramer
Kenneth L
KL
Center for Children, Huntsman Cancer Institute, Department of Oncological Sciences, University of Utah, Salt Lake City 84112, USA.
Barnette
Janet E
JE
Yost
H Joseph
HJ
D000818:Animals; D019521:Body Patterning / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D004475:Ectoderm / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology*; D005775:Gastrula / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D053669:Syndecan-2; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology* / Q000378:metabolism
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D029867:Xenopus Proteins; C508248:sdc2 protein, Xenopus; D053669:Syndecan-2; C087857:protein kinase C gamma; D011493:Protein Kinase C