Three-tier regulation of cell number plasticity by neurotrophins and Tolls in Drosophila

Istvan Foldi, Niki Anthoney, Neale Harrison, Monique Gangloff, Brett Verstak, Mohanakarthik Ponnadai Nallasivan, Samaher AlAhmed, Bangfu Zhu, Mark Phizacklea, Maria Losada-Perez, Marta Moreira, Nicholas J. Gay, Alicia Hidalgo*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

15 Citations (Scopus)
251 Downloads (Pure)

Abstract

Cell number plasticity is coupled to circuitry in the nervous system, adjusting cell mass to functional requirements. In mammals, this is achieved by neurotrophin (NT) ligands, which promote cell survival via their Trk and p75NTR receptors and cell death via p75NTR and Sortilin. Drosophila NTs (DNTs) bind Toll receptors instead to promote neuronal survival, but whether they can also regulate cell death is unknown. In this study, we show that DNTs and Tolls can switch from promoting cell survival to death in the central nervous system (CNS) via a three-tier mechanism. First, DNT cleavage patterns result in alternative signaling outcomes. Second, different Tolls can preferentially promote cell survival or death. Third, distinct adaptors downstream of Tolls can drive either apoptosis or cell survival. Toll-6 promotes cell survival via MyD88-NF-κB and cell death via Wek-Sarm-JNK. The distribution of adaptors changes in space and time and may segregate to distinct neural circuits. This novel mechanism for CNS cell plasticity may operate in wider contexts.

Original languageEnglish
Pages (from-to)1421-1438
Number of pages18
JournalJournal of Cell Biology
Volume216
Issue number5
DOIs
Publication statusPublished - 1 May 2017

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