TORC1 regulation of dendrite regrowth after pruning is linked to actin and exocytosis

PLoS Genet. 2023 May 11;19(5):e1010526. doi: 10.1371/journal.pgen.1010526. eCollection 2023 May.

Abstract

Neurite pruning and regrowth are important mechanisms to adapt neural circuits to distinct developmental stages. Neurite regrowth after pruning often depends on differential regulation of growth signaling pathways, but their precise mechanisms of action during regrowth are unclear. Here, we show that the PI3K/TORC1 pathway is required for dendrite regrowth after pruning in Drosophila peripheral neurons during metamorphosis. TORC1 impinges on translation initiation, and our analysis of 5' untranslated regions (UTRs) of remodeling factor mRNAs linked to actin suggests that TOR selectively stimulates the translation of regrowth over pruning factors. Furthermore, we find that dendrite regrowth also requires the GTPase RalA and the exocyst complex as regulators of polarized secretion, and we provide evidence that this pathway is also regulated by TOR. We propose that TORC1 coordinates dendrite regrowth after pruning by coordinately stimulating the translation of regrowth factors involved in cytoskeletal regulation and secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Dendrites / physiology
  • Drosophila / metabolism
  • Drosophila Proteins* / metabolism
  • Exocytosis
  • Mechanistic Target of Rapamycin Complex 1 / metabolism
  • Monomeric GTP-Binding Proteins* / metabolism
  • Neurites / metabolism

Substances

  • Actins
  • Drosophila Proteins
  • Mechanistic Target of Rapamycin Complex 1
  • Monomeric GTP-Binding Proteins
  • RalA protein, Drosophila
  • CRTC protein, Drosophila

Grants and funding

This work was supported by grant RU1673/6-1 from the Deutsche Forschungsgemeinschaft (DFG) and the Collaborative Research Center CRC1348 (project B04) to SR. NS was supported by the Cells-in-Motion (EXC1003) graduate school and Cells-in-Motion bridging funds. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.