Alexandre Chaumet1, Graham D. Wright2,4, Sze Hwee Seet1, Keit Min Tham1, Natalia V. Gounko1,2,4 and Frederic Bard1,3*.
1 Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673
2 Institute of Medical Biology, 8A Biomedical Grove, #06-06 Immunos, Singapore 138648
3 Department of Biochemistry, National University of Singapore, 21 Lower Kent Ridge Road, Singapore 119077
4 Joint IMB-IMCB Electron Microscopy Suite, 20 Biopolis Street, #B2-14 Matrix Singapore 138671
* Corresponding Author
Published in Nature Communications on 10 September 2015.
Please click here to read the full article.
In this study, we describe a novel trafficking pathway that links the cell surface to the nucleus.
Typically, cell surface material is endocytosed and transported for internal degradation. We show that a new type of endosomes instead targets molecules to the nucleus. At least two molecules, a cell surface protein that drives cell proliferation in cancer, the EGF-receptor, and a bacterial toxin, the Pseudomonas exotoxin A, use this pathway. Interestingly, nuclear localization of EGF-R has been associated with cancer relapse and poor prognosis. This study provides a paradigm shift and explains how external molecules can reach directly the core of the cell and regulate the expression of genes. Controlling this Nuclear-Associated Endosomes (NAE) pathway could help combat cancer relapse or infectious diseases as well as open the door to a new class of therapeutic agents, able to target directly the DNA of cells.
Figure legend: Two intracellular routes of cargos. After endocytosis, NAE dock on the nucleus, discharging their content into the nucleoplasm in a SUN1/2- and Sec61 translocon-dependent manner.
For more information on Frederic BARD’s laboratory, please click here.