A Nup133-dependent NPC-anchored network tethers centrosomes to the nuclear envelope in prophase

Stéphanie Bolhy; Imène Bouhlel; Elisa Dultz; Tania Nayak; Michela Zuccolo; Xavier Gatti; Richard Vallee; Jan Ellenberg; Valérie Doye

doi:10.1083/jcb.201007118

A Nup133-dependent NPC-anchored network tethers centrosomes to the nuclear envelope in prophase

J Cell Biol. 2011 Mar 7;192(5):855-71. doi: 10.1083/jcb.201007118.

Authors

Stéphanie Bolhy¹, Imène Bouhlel, Elisa Dultz, Tania Nayak, Michela Zuccolo, Xavier Gatti, Richard Vallee, Jan Ellenberg, Valérie Doye

Affiliation

¹ Cell Biology Program, Institut Jacques Monod, UMR 7592 Centre National de la Recherche Scientifique-Université Paris Diderot, 75205 Paris Cedex 13, France.

Abstract

Centrosomes are closely associated with the nuclear envelope (NE) throughout the cell cycle and this association is maintained in prophase when they separate to establish the future mitotic spindle. At this stage, the kinetochore constituents CENP-F, NudE, NudEL, dynein, and dynactin accumulate at the NE. We demonstrate here that the N-terminal domain of the nuclear pore complex (NPC) protein Nup133, although largely dispensable for NPC assembly, is required for efficient anchoring of the dynein/dynactin complex to the NE in prophase. Nup133 exerts this function through an interaction network via CENP-F and NudE/EL. We show that this molecular chain is critical for maintaining centrosome association with the NE at mitotic entry and contributes to this process without interfering with the previously described RanBP2-BICD2-dependent pathway of centrosome anchoring. Finally, our study reveals that tethering of centrosomes to the nuclear surface at the G2/M transition contributes, along with other cellular mechanisms, to early stages of bipolar spindle assembly.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carrier Proteins / metabolism
Carrier Proteins / physiology
Cell Line, Tumor
Cell Polarity
Centrosome / metabolism*
Centrosome / ultrastructure
Chromosomal Proteins, Non-Histone / metabolism
Chromosomal Proteins, Non-Histone / physiology
Dynactin Complex
Dyneins / metabolism
HeLa Cells
Humans
Intranuclear Space / metabolism
Intranuclear Space / ultrastructure
Microfilament Proteins / metabolism
Microfilament Proteins / physiology
Microtubule-Associated Proteins / metabolism
Minor Histocompatibility Antigens
Nuclear Envelope / metabolism*
Nuclear Envelope / ultrastructure
Nuclear Pore / metabolism*
Nuclear Pore Complex Proteins / chemistry
Nuclear Pore Complex Proteins / metabolism
Nuclear Pore Complex Proteins / physiology*
Prophase*
Protein Interaction Mapping
Spindle Apparatus / metabolism

Substances

Carrier Proteins
Chromosomal Proteins, Non-Histone
Dynactin Complex
Microfilament Proteins
Microtubule-Associated Proteins
Minor Histocompatibility Antigens
NDEL1 protein, human
NUP133 protein, human
Nuclear Pore Complex Proteins
centromere protein F
Dyneins