GCL and CUL3 Control the Switch between Cell Lineages by Mediating Localized Degradation of an RTK.

TitleGCL and CUL3 Control the Switch between Cell Lineages by Mediating Localized Degradation of an RTK.
Publication TypeJournal Article
Year of Publication2017
AuthorsPae J, Cinalli RM, Marzio A, Pagano M, Lehmann R
JournalDev Cell
Volume42
Issue2
Pagination130-142.e7
Date Published2017 07 24
ISSN1878-1551
KeywordsAnimals, Cell Lineage, Cell Membrane, Conserved Sequence, Cullin Proteins, Drosophila melanogaster, Drosophila Proteins, Germ Cells, HEK293 Cells, Humans, Intercellular Signaling Peptides and Proteins, Mitosis, Nuclear Envelope, Nuclear Localization Signals, Nuclear Proteins, Oogenesis, Protein Domains, Proteolysis, Receptor Protein-Tyrosine Kinases, Signal Transduction, Substrate Specificity, Ubiquitination
Abstract

The separation of germline from somatic lineages is fundamental to reproduction and species preservation. Here, we show that Drosophila Germ cell-less (GCL) is a critical component in this process by acting as a switch that turns off a somatic lineage pathway. GCL, a conserved BTB (Broad-complex, Tramtrack, and Bric-a-brac) protein, is a substrate-specific adaptor for Cullin3-RING ubiquitin ligase complex (CRL3GCL). We show that CRL3GCL promotes PGC fate by mediating degradation of Torso, a receptor tyrosine kinase (RTK) and major determinant of somatic cell fate. This mode of RTK degradation does not depend upon receptor activation but is prompted by release of GCL from the nuclear envelope during mitosis. The cell-cycle-dependent change in GCL localization provides spatiotemporal specificity for RTK degradation and sequesters CRL3GCL to prevent it from participating in excessive activities. This precisely orchestrated mechanism of CRL3GCL function and regulation defines cell fate at the single-cell level.

DOI10.1016/j.devcel.2017.06.022
Alternate JournalDev Cell
PubMed ID28743001
PubMed Central IDPMC5568677
Grant ListR37 HD041900 / HD / NICHD NIH HHS / United States
R01 GM057587 / GM / NIGMS NIH HHS / United States
/ HHMI / Howard Hughes Medical Institute / United States
P40 OD018537 / OD / NIH HHS / United States
R37 CA076584 / CA / NCI NIH HHS / United States
R01 CA076584 / CA / NCI NIH HHS / United States
T32 CA160002 / CA / NCI NIH HHS / United States
R21 CA202200 / CA / NCI NIH HHS / United States
R01 HD041900 / HD / NICHD NIH HHS / United States
Related Faculty: 
Antonio Marzio, Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
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