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

Publication date: 24 July 2017
Source:Developmental Cell, Volume 42, Issue 2
Author(s): Juhee Pae, Ryan M. Cinalli, Antonio Marzio, Michele Pagano, Ruth Lehmann
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 (CRL3^GCL). We show that CRL3^GCL 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 CRL3^GCL to prevent it from participating in excessive activities. This precisely orchestrated mechanism of CRL3^GCL function and regulation defines cell fate at the single-cell level.

Graphical abstract

Teaser

Primordial germ cells (PGCs) ensure continuity of life through generations. Combining genetic and biochemical analysis, Pae et al. show that GCL and CUL3 promote PGC formation by targeting the Torso RTK for ubiquitylation and degradation. Cell-cycle-dependent regulation of GCL subcellular localization confers spatiotemporal control of the Torso pathway.


from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2v3pN2r