Role of PKA as a negative regulator of PCP signaling pathway during Xenopus gastrulation movements.
Convergent extension (CE) movements in gastrulation are essential for the establishment of the body axis during early vertebrate development. Although the precise molecular mechanisms of CE movements are not clearly understood, noncanonical Wnt pathway is known to be important for the control of CE movements. Here, we present evidence that PKA is implicated in noncanonical Wnt pathway. Overexpression and specific depletion of PKA inhibit CE movements. PKA depletion also disrupts cell morphology, protrusive activity, and cortical actin formation in dorsal mesodermal cells. Moreover, PKA activity is negatively regulated by major components of planar cell polarity (PCP) pathway. In line with this, overexpression of PKA can rescue the inhibition of CE movements caused by overexpression of these molecules. We also demonstrate that this regulation of PKA activity is dependent upon Galphai signaling. As a negative component of PCP signaling, PKA inhibits not only the activation of RhoA and JNK but also the Dsh-Daam1-RhoA complex formation which is essential for the regulation of RhoA activity. Together, our study suggests a molecular pathway from Wnt/Dsh/PKA signaling to Rho activation in PCP signaling.
Park
Eunjoo
E
Division of Molecular and Life Sciences, Pohang University of Science and Technology, San 31, Hyoja-dong, Pohang, Kyungbuk 790-784, South Korea.
Kim
Gun-Hwa
GH
Choi
Sun-Cheol
SC
Han
Jin-Kwan
JK
D000818:Animals; D016764:Cell Polarity; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D005775:Gastrula; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D015398:Signal Transduction; D014981:Xenopus / Q000196:embryology*
D017868:Cyclic AMP-Dependent Protein Kinases