RRC ID 64509
Author Ariss MM, Terry AR, Islam ABMMK, Hay N, Frolov MV.
Title Amalgam regulates the receptor tyrosine kinase pathway through Sprouty in glial cell development in the Drosophila larval brain.
Journal J Cell Sci
Abstract The receptor tyrosine kinase (RTK) pathway plays an essential role in development and disease by controlling cell proliferation and differentiation. Here, we profile the Drosophila larval brain by single-cell RNA-sequencing and identify Amalgam (Ama), which encodes a cell adhesion protein of the immunoglobulin IgLON family, as regulating the RTK pathway activity during glial cell development. Depletion of Ama reduces cell proliferation, affects glial cell type composition and disrupts the blood-brain barrier (BBB), which leads to hemocyte infiltration and neuronal death. We show that Ama depletion lowers RTK activity by upregulating Sprouty (Sty), a negative regulator of the RTK pathway. Knockdown of Ama blocks oncogenic RTK signaling activation in the Drosophila glioma model and halts malignant transformation. Finally, knockdown of a human ortholog of Ama, LSAMP, results in upregulation of SPROUTY2 in glioblastoma cell lines, suggesting that the relationship between Ama and Sty is conserved.
Volume 133(19)
Published 2020-10-1
DOI 10.1242/jcs.250837
PII jcs.250837
PMID 32878945
PMC PMC7541346
MeSH Animals Brain / metabolism Drosophila* / metabolism Drosophila Proteins / genetics* Gene Expression Regulation, Developmental Immunoglobulins / genetics* Larva / metabolism Membrane Proteins / genetics* Membrane Proteins / metabolism Neuroglia / metabolism Receptor Protein-Tyrosine Kinases / genetics Receptor Protein-Tyrosine Kinases / metabolism
IF 4.573
Drosophila DGRC#103970