Regulation of Notch signalling by non-visual beta-arrestin.
Signalling activity of the Notch receptor, which plays a fundamental role in metazoan cell fate determination, is controlled at multiple levels. We uncovered a Notch signal-controlling mechanism that depends on the ability of the non-visual beta-arrestin, Kurtz (Krz), to influence the degradation and, consequently, the function of the Notch receptor. We identified Krz as a binding partner of a known Notch-pathway modulator, Deltex (Dx), and demonstrated the existence of a trimeric Notch-Dx-Krz protein complex. This complex mediates the degradation of the Notch receptor through a ubiquitination-dependent pathway. Our results establish a novel mode of regulation of Notch signalling and define a new function for non-visual beta-arrestins.
Mukherjee
Ashim
A
Department of Cell Biology, Harvard Medical School, Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.
Veraksa
Alexey
A
Bauer
Andreas
A
Rosse
Carine
C
Camonis
Jacques
J
Artavanis-Tsakonas
Spyros
S
D000818:Animals; D019390:Arrestins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005260:Female; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D046912:Multiprotein Complexes; D009154:Mutation / Q000502:physiology; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000378:metabolism; D014921:Wings, Animal / Q000254:growth & development; D000071557:beta-Arrestins
D019390:Arrestins; C086679:DX protein, Drosophila; D029721:Drosophila Proteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; C497759:N protein, Drosophila; D051880:Receptors, Notch; D025801:Ubiquitin; D000071557:beta-Arrestins; C412169:krz protein, Drosophila