Nuclear Pores: Transport and Cell Cycle

Valérie Doye was awarded the CNRS Silver Medal for 2009

Nuclear Pore Complexes (NPCs) are elaborate structures embedded in the nuclear envelope and composed of multiple copies of about 30 different proteins termed nucleoporins (Nups) (Figure 1). Our team aims at characterizing, beyond their well-established function in transport between the cytoplasm and the nucleus, non-conventional functions of NPCs and nucleoporins in nuclear metabolism and during mitosis.
To understand these fundamental processes, our projects are mainly focused on an evolutionarily conserved NPC sub-complex, called Nup107-160 in mammalian cells (Figure 1) and Nup84 in the yeast S. cerevisiae. For this purpose, we combine live-cell imaging, genetics and biochemistry.

 

Over these last years, our studies have revealed the key function of the vertebrate Nup107-160 complex in NPC re-assembly at mitotic exit, its recruitment at kinetochores, where it is required for proper chromosome segregation (Figure 2), and its implication in cell differentiation during early embryogenesis (coll. with L. Lacy, NY, USA). In addition, a genetic screen in yeast revealed functional connections between the Nup84 complex, sumoylation processes and DNA repair, and uncovered previously uncharacterized proteins, Pom33 and Pml39, respectively involved in NPC biogenesis and regulation of mRNA export (Figures 3 & 4).

Current Research Topics:

• Nuclear Pore assembly in yeast and vertebrates
• The vertebrate Nup107-160 complex and its partners: implication in mitotic progression
• Molecular mechanisms underlying the function of Nup133 in cell differentiation
• mRNA export regulation in yeast
• NPC-dependent regulation of SUMOylation processes

Sélection of Publications

Bolhy S, Bouhlel I, Dultz E, Nayak T, Zuccolo M, Gatti X, Vallee R, Ellenberg J, Doye V.
A Nup133-dependent NPC-anchored network tethers centrosomes to the nuclear envelope in prophase.
J Cell Biol. 2011 Mar 7;192(5):855-71.
Abstract
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Chadrin A., Hess B., San Roman M., Gatti X., Lombard B., Loew D., Barral Y., Palancade B., Doye V. (2010)
Pom33, a novel transmembrane nucleoporin required for proper nuclear pore complex distribution.
J Cell Biol. 189:795-811.
Abstract

Lupu F, Alves A, Anderson K, Doye V, Lacy E.
Nuclear pore composition regulates neural stem/progenitor cell differentiation in the mouse embryo.
Dev Cell. 2008 Jun;14(6):831-42.
Abstract

Palancade B, Liu X, Garcia-Rubio M, Aguilera A, Zhao X, Doye V.
Nucleoporins prevent DNA damage accumulation by modulating Ulp1-dependent sumoylation processes.
Mol Biol Cell. 2007 Aug;18(8):2912-23.
Abstract

Zuccolo M, Alves A, Galy V, Bolhy S, Formstecher E, Racine V, Sibarita JB, Fukagawa T, Shiekhattar R, Yen T, Doye V.
The human Nup107-160 nuclear pore subcomplex contributes to proper kinetochore functions.
EMBO J. 2007 Apr 4;26(7):1853-64.
Abstract

Last modified 03/29/2011

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