Gcm protein degradation suppresses proliferation of glial progenitors.
Gliogenesis in animal development is spatiotemporally regulated so that correct numbers of glia are present to support various neuronal functions. During Drosophila embryonic development, the glial regulatory gene, glial cell missing/glial cell deficient (gcm/glide), promotes glial cell fate and differentiation. Here we describe the ubiquitin-proteasome regulation of the Gcm protein and the consequence in gliogenesis without timely degradation of Gcm. Gcm binds to 2 F-box proteins, Supernumerary limbs (Slimb) and Archipelago (Ago), adaptors of SCF E3 ubiquitin ligases. Ubiquitination and proteasomal degradation of Gcm depend on slimb and ago. In slimb and ago double mutants, Gcm protein levels are enhanced. Concomitantly, glial cell numbers increase owing to proliferation, which can be phenocopied by Gcm overexpression only at the onset of glial differentiation. The glial lineage 5-6A in slimb ago mutants displays excess glial progenies and enhanced Gcm protein levels. We propose that downregulation of Gcm protein levels by Slimb and Ago is required for glial progenitors to exit the cell cycle for differentiation.
Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 115, Taiwan.
Margaret Su-chun
MS
Ho
Hungwen
H
Chen
Minghan
M
Chen
Cécile
C
Jacques
Angela
A
Giangrande
Cheng-Ting
CT
Chien
D000818:Animals; D019070:Cell Lineage; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D044783:F-Box Proteins / Q000378:metabolism; D018628:Gene Dosage; D009154:Mutation / Q000235:genetics; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism*; D010641:Phenotype; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D013489:Suppression, Genetic; D014157:Transcription Factors / Q000378:metabolism*; D054875:Ubiquitination
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D044783:F-Box Proteins; C102805:GCM protein, Drosophila; D014157:Transcription Factors; D046988:Proteasome Endopeptidase Complex