A proteomic approach to identify endosomal cargoes controlling cancer invasiveness

We have previously shown that Rab17 - a small GTPase associated with epithelial polarity - is specifically suppressed by ERK2 signalling to promote an invasive phenotype. However, the mechanisms through which Rab17 loss permits invasiveness, and the endosomal cargoes that are responsible for mediating this are not known. Using quantitative mass spectrometry-based proteomics, we have found that knockdown of Rab17 leads to highly selective reduction in the cellular levels of a v-SNARE (Vamp8). Moreover, proteomics and immunofluorescence indicate that Vamp-8 is associated with Rab17 at late endosomes. Reduced levels of Vamp8 promote transition between ductal carcinoma in situ (DCIS) and a more invasive phenotype. We developed an unbiased proteomic approach to elucidate the complement of receptors that redistributes between endosomes and the plasma membrane, and have pin-pointed neuropilin-2 (NRP2) as a key pro-invasive cargo of Rab17/Vamp8-regulated trafficking. Indeed, reduced Rab17 or Vamp8 levels lead to increased mobilisation of NRP2-containing late endosomes and upregulated cell surface expression of NRP2. Finally, we show that NRP2 is required for the basement membrane disruption which accompanies transition between DCIS and a more invasive phenotype

Amphibisches Flugboot (AFB) neuer Generation im Rahmen der EUREKA-Initiative. Phase 1: Technologie- und Demonstrator-Definitionsphase. Bd. 1 Zusammenfassung. Schlussbericht

In cooperation with Aeritalia - based on many years of experience in flying boat construction, recently also with the ATT Amphibious Technology Carrier -Dornier has developed the requirements and concept for an advanced amphibious flying boat. This involved determining and investigating the following essential technology priorities: hydromechanics for seaplanes; hydrofoil; materials, structures, surface protection; aerodynamics; avionics, mission equipment; system analysis. (orig.)SIGLEAvailable from TIB Hannover: RR 5028(1990,113) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

ISOPHOT. Phase C/D Abschlussbericht

Available from TIB Hannover: F98B1273+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman