Title | GCL and CUL3 Control the Switch between Cell Lineages by Mediating Localized Degradation of an RTK. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Pae J, Cinalli RM, Marzio A, Pagano M, Lehmann R |
Journal | Dev Cell |
Volume | 42 |
Issue | 2 |
Pagination | 130-142.e7 |
Date Published | 2017 07 24 |
ISSN | 1878-1551 |
Keywords | Animals, 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. |
DOI | 10.1016/j.devcel.2017.06.022 |
Alternate Journal | Dev Cell |
PubMed ID | 28743001 |
PubMed Central ID | PMC5568677 |
Grant List | R37 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 Lab:
Related Faculty:
Antonio Marzio, Ph.D.