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Dev Cell. 2017 Jul 24;42(2):130-142.e7. doi: 10.1016/j.devcel.2017.06.022.

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

Author information

1
HHMI and Kimmel Center for Biology and Medicine of the Skirball Institute, Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
2
HHMI, Department of Biochemistry and Molecular Pharmacology and Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA.
3
HHMI and Kimmel Center for Biology and Medicine of the Skirball Institute, Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA. Electronic address: ruth.lehmann@med.nyu.edu.

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.

KEYWORDS:

CUL3; GCL; RTK; germ cell; germ cell-less; germline; nuclear lamina; protein degradation; receptor tyrosine kinase; ubiquitin

PMID:
28743001
PMCID:
PMC5568677
DOI:
10.1016/j.devcel.2017.06.022
[Indexed for MEDLINE]
Free PMC Article

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