TY - JOUR
T1 - Three-tier regulation of cell number plasticity by neurotrophins and Tolls in Drosophila
AU - Foldi, Istvan
AU - Anthoney, Niki
AU - Harrison, Neale
AU - Gangloff, Monique
AU - Verstak, Brett
AU - Nallasivan, Mohanakarthik Ponnadai
AU - AlAhmed, Samaher
AU - Zhu, Bangfu
AU - Phizacklea, Mark
AU - Losada-Perez, Maria
AU - Moreira, Marta
AU - Gay, Nicholas J.
AU - Hidalgo, Alicia
PY - 2017/5/1
Y1 - 2017/5/1
N2 - 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.
AB - 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.
U2 - 10.1083/jcb.201607098
DO - 10.1083/jcb.201607098
M3 - Article (Academic Journal)
C2 - 28373203
AN - SCOPUS:85021803701
VL - 216
SP - 1421
EP - 1438
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 5
ER -