Small GTPase Rab5 participates in chromosome congression and regulates localization of the centromere-associated protein CENP-F to kinetochores

Gaetana Serio, Valentina Margaria, Sanne Jensen, Amanda Oldani, Jiri Bartek, Federico Bussolino, Letizia Lanzetti

Research output: Contribution to journalArticle

Abstract

Rab5 is a small GTPase known to regulate vesicular trafficking during interphase. Here, we show that Rab5 also plays an unexpected role during mitotic progression. RNAi-mediated silencing of Rab5 caused defects in chromosome congression and extensive prometaphase delay, and it correlated with a severe reduction in the localization of the centromere-associated protein CENP-F to kinetochores. CENP-F is a component of the nuclear matrix required for chromosome congression that, at mitotic entry, localizes to the nuclear envelope and assembles on kinetochores, contributing to the establishment of kinetochore microtubule interactions. We found that Rab5 forms a complex with a subset of CENP-F in mitotic cells and regulates the kinetics of release of CENP-F from the nuclear envelope and its accumulation on kinetochores. Simultaneous depletion of both Rab5 and CENP-F recapitulated the mitotic defects caused by silencing of either Rab5 or CENP-F alone, indicating epistatic roles for these two proteins in the pathway that orchestrates chromosome congression. These results reveal the involvement of Rab5 in the proper execution of mitotic programs whose deregulation can undermine chromosomal stability.

Original languageEnglish
Pages (from-to)17337-17342
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number42
DOIs
Publication statusPublished - Oct 18 2011

Fingerprint

Kinetochores
Monomeric GTP-Binding Proteins
Centromere
Chromosomes
Nuclear Envelope
Prometaphase
Nuclear Matrix
Chromosomal Instability
Interphase
RNA Interference
Microtubules
centromere protein F
Proteins

Keywords

  • Endocytosis
  • Mitosis

ASJC Scopus subject areas

  • General

Cite this

Small GTPase Rab5 participates in chromosome congression and regulates localization of the centromere-associated protein CENP-F to kinetochores. / Serio, Gaetana; Margaria, Valentina; Jensen, Sanne; Oldani, Amanda; Bartek, Jiri; Bussolino, Federico; Lanzetti, Letizia.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 42, 18.10.2011, p. 17337-17342.

Research output: Contribution to journalArticle

@article{42ecc6205e1844bdaedb8a9221a06841,
title = "Small GTPase Rab5 participates in chromosome congression and regulates localization of the centromere-associated protein CENP-F to kinetochores",
abstract = "Rab5 is a small GTPase known to regulate vesicular trafficking during interphase. Here, we show that Rab5 also plays an unexpected role during mitotic progression. RNAi-mediated silencing of Rab5 caused defects in chromosome congression and extensive prometaphase delay, and it correlated with a severe reduction in the localization of the centromere-associated protein CENP-F to kinetochores. CENP-F is a component of the nuclear matrix required for chromosome congression that, at mitotic entry, localizes to the nuclear envelope and assembles on kinetochores, contributing to the establishment of kinetochore microtubule interactions. We found that Rab5 forms a complex with a subset of CENP-F in mitotic cells and regulates the kinetics of release of CENP-F from the nuclear envelope and its accumulation on kinetochores. Simultaneous depletion of both Rab5 and CENP-F recapitulated the mitotic defects caused by silencing of either Rab5 or CENP-F alone, indicating epistatic roles for these two proteins in the pathway that orchestrates chromosome congression. These results reveal the involvement of Rab5 in the proper execution of mitotic programs whose deregulation can undermine chromosomal stability.",
keywords = "Endocytosis, Mitosis",
author = "Gaetana Serio and Valentina Margaria and Sanne Jensen and Amanda Oldani and Jiri Bartek and Federico Bussolino and Letizia Lanzetti",
year = "2011",
month = "10",
day = "18",
doi = "10.1073/pnas.1103516108",
language = "English",
volume = "108",
pages = "17337--17342",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "42",

}

TY - JOUR

T1 - Small GTPase Rab5 participates in chromosome congression and regulates localization of the centromere-associated protein CENP-F to kinetochores

AU - Serio, Gaetana

AU - Margaria, Valentina

AU - Jensen, Sanne

AU - Oldani, Amanda

AU - Bartek, Jiri

AU - Bussolino, Federico

AU - Lanzetti, Letizia

PY - 2011/10/18

Y1 - 2011/10/18

N2 - Rab5 is a small GTPase known to regulate vesicular trafficking during interphase. Here, we show that Rab5 also plays an unexpected role during mitotic progression. RNAi-mediated silencing of Rab5 caused defects in chromosome congression and extensive prometaphase delay, and it correlated with a severe reduction in the localization of the centromere-associated protein CENP-F to kinetochores. CENP-F is a component of the nuclear matrix required for chromosome congression that, at mitotic entry, localizes to the nuclear envelope and assembles on kinetochores, contributing to the establishment of kinetochore microtubule interactions. We found that Rab5 forms a complex with a subset of CENP-F in mitotic cells and regulates the kinetics of release of CENP-F from the nuclear envelope and its accumulation on kinetochores. Simultaneous depletion of both Rab5 and CENP-F recapitulated the mitotic defects caused by silencing of either Rab5 or CENP-F alone, indicating epistatic roles for these two proteins in the pathway that orchestrates chromosome congression. These results reveal the involvement of Rab5 in the proper execution of mitotic programs whose deregulation can undermine chromosomal stability.

AB - Rab5 is a small GTPase known to regulate vesicular trafficking during interphase. Here, we show that Rab5 also plays an unexpected role during mitotic progression. RNAi-mediated silencing of Rab5 caused defects in chromosome congression and extensive prometaphase delay, and it correlated with a severe reduction in the localization of the centromere-associated protein CENP-F to kinetochores. CENP-F is a component of the nuclear matrix required for chromosome congression that, at mitotic entry, localizes to the nuclear envelope and assembles on kinetochores, contributing to the establishment of kinetochore microtubule interactions. We found that Rab5 forms a complex with a subset of CENP-F in mitotic cells and regulates the kinetics of release of CENP-F from the nuclear envelope and its accumulation on kinetochores. Simultaneous depletion of both Rab5 and CENP-F recapitulated the mitotic defects caused by silencing of either Rab5 or CENP-F alone, indicating epistatic roles for these two proteins in the pathway that orchestrates chromosome congression. These results reveal the involvement of Rab5 in the proper execution of mitotic programs whose deregulation can undermine chromosomal stability.

KW - Endocytosis

KW - Mitosis

UR - http://www.scopus.com/inward/record.url?scp=80054819304&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80054819304&partnerID=8YFLogxK

U2 - 10.1073/pnas.1103516108

DO - 10.1073/pnas.1103516108

M3 - Article

C2 - 21987812

AN - SCOPUS:80054819304

VL - 108

SP - 17337

EP - 17342

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 42

ER -