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Endosomal sorting of Notch receptors through COMMD9-dependent pathways modulates Notch signaling.

Authors :
Haiying Li
Yeon Koo
Xicheng Mao
Sifuentes-Dominguez, Luis
Morris, Lindsey L.
Da Jia
Naoteru Miyata
Faulkner, Rebecca A.
van Deursen, Jan M.
Vooijs, Marc
Billadeau, Daniel D.
van de Sluis, Bart
Cleaver, Ondine
Burstein, Ezra
Source :
Journal of Cell Biology. 11/9/2015, Vol. 211 Issue 3, p605-617. 13p.
Publication Year :
2015

Abstract

Notch family members are transmembrane receptors that mediate essential developmental programs. Upon ligand binding, a proteolytic event releases the intracellular domain of Notch, which translocates to the nucleus to regulate gene transcription. In addition, Notch trafficking across the endolysosomal system is critical in its regulation. In this study we report that Notch recycling to the cell surface is dependent on the COMMD-CCDC22-CCDC93 (CCC) complex, a recently identified regulator of endosomal trafficking. Disruption in this system leads to intracellular accumulation of Notch2 and concomitant reduction in Notch signaling. Interestingly, among the 10 copper metabolism MURR1 domain containing (COMMD) family members that can associate with the CCC complex, only COMMD9 and its binding partner, COMMD5, have substantial effects on Notch. Furthermore, Commd9 deletion in mice leads to embryonic lethality and complex cardiovascular alterations that bear hallmarks of Notch deficiency. Altogether, these studies highlight that the CCC complex controls Notch activation by modulating its intracellular trafficking and demonstrate cargo-specific effects for members of the COMMD protein family. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00219525
Volume :
211
Issue :
3
Database :
Academic Search Index
Journal :
Journal of Cell Biology
Publication Type :
Academic Journal
Accession number :
110907245
Full Text :
https://doi.org/10.1083/jcb.201505108