Pair-wise regulation of convergence and extension cell movements by four phosphatases via RhoA.

ABSTRACT: Various signaling pathways regulate shaping of the main body axis during early vertebrate development. Here, we focused on the role of protein-tyrosine phosphatase signaling in convergence and extension cell movements. We identified Ptpn20 as a structural paralogue of PTP-BL and both phosphatases were required for normal gastrulation cell movements. Interestingly, knockdowns of PTP-BL and Ptpn20 evoked similar developmental defects as knockdown of RPTP? and PTP?. Co-knockdown of RPTP? and PTP-BL, but not Ptpn20, had synergistic effects and conversely, PTP? and Ptpn20, but not PTP-BL, cooperated, demonstrating the specificity of our approach. RPTP? and PTP? knockdowns were rescued by constitutively active RhoA, whereas PTP-BL and Ptpn20 knockdowns were rescued by dominant negative RhoA. Consistently, RPTP? and PTP-BL had opposite effects on RhoA activation, both in a PTP-dependent manner. Downstream of the PTPs, we identified NGEF and Arhgap29, regulating RhoA activation and inactivation, respectively, in convergence and extension cell movements. We propose a model in which two phosphatases activate RhoA and two phosphatases inhibit RhoA, resulting in proper cell polarization and normal convergence and extension cell movements.

SUBMITTER: van Eekelen M 

PROVIDER: S-EPMC3335823 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature