title: Gβγ signaling controls the polarization of zebrafish primordial germ cells by regulating Rac activity.
abstract: During development, primordial germ cells (PGCs) migrate from the sites of their specification towards the region in which the future gonad develops. This cell migration requires polarization of PGCs and their responsiveness to external guidance cues. In zebrafish, the directed migration and polarization of PGCs are regulated independently, by the chemokine Cxcl12a and the Rho GTPase Rac1, respectively. However, the upstream signals controlling Rac activity in this context have not yet been identified. By investigating the role of G proteins in PGC migration, we found that signaling mediated by G protein subunits Gβγ is required to regulate cell polarization. PGCs that are defective for Gβγ signaling failed to polarize, and developed multiple protrusions in random locations, resembling the defects observed in PGCs with decreased Rac activity. These defects render PGCs incapable of migrating actively and responding to directional cues. FRET-based assays showed that PGCs require Gβγ signaling for polarized Rac activation and actin organization at the leading front, as well as for maintaining overall Rac levels in these cells. Conversely, overexpression of Gβγ in PGCs increases Rac activity. Our results indicate that during PGC migration in vivo, Gβγ signaling regulates Rac activity to control cell polarity, which is required for the responsiveness to chemokine signaling.
authors.affiliation: Department of Anatomy and Cell Biology, University of Iowa, 1-400 Bowen Science Building, 51 Newton Road, Iowa City, IA 52242-1109, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Elena
authors.initials: E
authors.lastname: Kardash
authors.forename: Songhai
authors.initials: S
authors.lastname: Chen
authors.forename: Erez
authors.initials: E
authors.lastname: Raz
authors.forename: Fang
authors.initials: F
authors.lastname: Lin
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology*; D054377:Chemokine CXCL12 / Q000378:metabolism; D003001:Cloning, Molecular; D031541:Fluorescence Resonance Energy Transfer; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism*; D044388:GTP-Binding Protein gamma Subunits / Q000378:metabolism*; D005854:Germ Cells / Q000502:physiology*; D006066:Gonads / Q000196:embryology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D059008:Time-Lapse Imaging; D015027:Zebrafish / Q000196:embryology*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; D054377:Chemokine CXCL12; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D020830:rac1 GTP-Binding Protein
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