Hedgehog signaling and Tre1 regulate actin dynamics through PI(4,5)P2 to direct migration of Drosophila embryonic germ cells

Ji Hoon Kim, Caitlin D. Hanlon, Sunaina Vohra, Peter N. Devreotes, Deborah J. Andrew

Research output: Contribution to journalArticlepeer-review

Abstract

The Tre1 G-protein coupled receptor (GPCR) was discovered to be required for Drosophila germ cell (GC) coalescence almost two decades ago, yet the molecular events both upstream and downstream of Tre1 activation remain poorly understood. To gain insight into these events, we describe a bona fide null allele and both untagged and tagged versions of Tre1. We find that the primary defect with complete Tre1 loss is the failure of GCs to properly navigate, with GC mis-migration occurring from early stages. We find that Tre1 localizes with F-actin at the migration front, along with PI(4,5)P2; dPIP5K, an enzyme that generates PI(4,5)P2; and dWIP, a protein that binds activated Wiskott-Aldrich syndrome protein (WASP), which stimulates F-actin polymerization. We show that Tre1 is required for polarized accumulation of F-actin, PI(4,5)P2, and dPIP5K. Smoothened also localizes with F-actin at the migration front, and Hh, through Smo, increases levels of Tre1 at the plasma membrane and Tre1’s association with dPIP5K. Kim et al. uncover molecular and cellular events upstream and downstream of the Tre1 G-protein coupled receptor (GPCR), which is required for germ cell navigation in Drosophila. Hedgehog signaling through Smoothened localizes Tre1 to activate F-actin assembly through dPIP5K, PI(4,5)P2, and WASP.

Original languageEnglish (US)
Article number108799
JournalCell Reports
Volume34
Issue number9
DOIs
StatePublished - Mar 2 2021

Keywords

  • cell migration
  • germ cells
  • GPCR
  • Hedgehog
  • PI(4,5)P
  • PIP5K
  • Smoothened
  • Tre1
  • WASP
  • WIP

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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