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

M. van Eekelen, V. Runtuwene, W. Masselink, J. den Hertog

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

Samenvatting

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 RPTPalpha and PTPepsilon. Co-knockdown of RPTPalpha and PTP-BL, but not Ptpn20, had synergistic effects and conversely, PTPepsilon and Ptpn20, but not PTP-BL, cooperated, demonstrating the specificity of our approach. RPTPalpha and PTPepsilon knockdowns were rescued by constitutively active RhoA, whereas PTP-BL and Ptpn20 knockdowns were rescued by dominant negative RhoA. Consistently, RPTPalpha 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.
Originele taal-2Engels
Pagina's (van-tot)35913
TijdschriftPLoS One
Volume7
Nummer van het tijdschrift4
DOI's
StatusGepubliceerd - 2012

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