TACC3-TSC2 maintains nuclear envelope structure and controls cell division

Laia Gómez-Baldó, Stephan Schmidt, Christopher A. Maxwell, Núria Bonifaci, Toni Gabaldón, Pierre Olivier Vidalain, William Senapedis, Anja Kletke, Mechthild Rosing, Angelika Barnekow, Robert Rottapel, Gabriel Capellá, Marc Vidal, Aristotelis Astreinidis, Roland P. Piekorz, Miguel Angel Pujana

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Studies of the role of tuberous sclerosis complex (TSC) proteins (TSC1/TSC2) in pathology have focused mainly on their capacity to regulate translation and cell growth, but their relationship with alterations of cellular structures and the cell cycle is not yet fully understood. the transforming acidic coiled-coil (TACC) domain-containing proteins are central players in structures and processes connected to the centrosome. Here, TACC3 interactome mapping identified TSC2 and 15 other physical interactors, including the evolutionary conserved interactions with ch-ToG/CKAP5 and FAM161B. TACC3 and TSC2 co-localize and co-purify with components of the nuclear envelope, and their deficiency causes morphological alterations of this structure. During cell division, TACC3 is necessary for the proper localization of phospho-Ser939 TSC2 at spindle poles and cytokinetic bridges. Accordingly, abscission alterations and increased frequency of binucleated cells were observed in Tacc3- and Tsc2-deficient cells relative to controls. In regulating cell division, TSC2 acts epistatically to TACC3 and, in addition to canonical TSC/mTOR signaling and cytokinetic associations, converges to the early mitotic checkpoint mediated by CHFR, consistently with nuclear envelope associations. our findings link TACC3 to novel structural and cell division functions of TSC2, which may provide additional explanations for the clinical and pathological manifestations of lymphangioleiomyomatosis (LAM) disease and tSC syndrome, including the greater clinical severity of TSC2 mutations compared to TSC1 mutations.

Original languageEnglish (US)
Pages (from-to)1143-1155
Number of pages13
JournalCell Cycle
Volume9
Issue number6
DOIs
StatePublished - Mar 15 2010
Externally publishedYes

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Nuclear Envelope
Cell Division
Tuberous Sclerosis
Lymphangioleiomyomatosis
Spindle Poles
M Phase Cell Cycle Checkpoints
Centrosome
Mutation
Cellular Structures
Cell Cycle
Pathology
Growth
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Gómez-Baldó, L., Schmidt, S., Maxwell, C. A., Bonifaci, N., Gabaldón, T., Vidalain, P. O., ... Pujana, M. A. (2010). TACC3-TSC2 maintains nuclear envelope structure and controls cell division. Cell Cycle, 9(6), 1143-1155. https://doi.org/10.4161/cc.9.6.11018

TACC3-TSC2 maintains nuclear envelope structure and controls cell division. / Gómez-Baldó, Laia; Schmidt, Stephan; Maxwell, Christopher A.; Bonifaci, Núria; Gabaldón, Toni; Vidalain, Pierre Olivier; Senapedis, William; Kletke, Anja; Rosing, Mechthild; Barnekow, Angelika; Rottapel, Robert; Capellá, Gabriel; Vidal, Marc; Astreinidis, Aristotelis; Piekorz, Roland P.; Pujana, Miguel Angel.

In: Cell Cycle, Vol. 9, No. 6, 15.03.2010, p. 1143-1155.

Research output: Contribution to journalArticle

Gómez-Baldó, L, Schmidt, S, Maxwell, CA, Bonifaci, N, Gabaldón, T, Vidalain, PO, Senapedis, W, Kletke, A, Rosing, M, Barnekow, A, Rottapel, R, Capellá, G, Vidal, M, Astreinidis, A, Piekorz, RP & Pujana, MA 2010, 'TACC3-TSC2 maintains nuclear envelope structure and controls cell division', Cell Cycle, vol. 9, no. 6, pp. 1143-1155. https://doi.org/10.4161/cc.9.6.11018
Gómez-Baldó L, Schmidt S, Maxwell CA, Bonifaci N, Gabaldón T, Vidalain PO et al. TACC3-TSC2 maintains nuclear envelope structure and controls cell division. Cell Cycle. 2010 Mar 15;9(6):1143-1155. https://doi.org/10.4161/cc.9.6.11018
Gómez-Baldó, Laia ; Schmidt, Stephan ; Maxwell, Christopher A. ; Bonifaci, Núria ; Gabaldón, Toni ; Vidalain, Pierre Olivier ; Senapedis, William ; Kletke, Anja ; Rosing, Mechthild ; Barnekow, Angelika ; Rottapel, Robert ; Capellá, Gabriel ; Vidal, Marc ; Astreinidis, Aristotelis ; Piekorz, Roland P. ; Pujana, Miguel Angel. / TACC3-TSC2 maintains nuclear envelope structure and controls cell division. In: Cell Cycle. 2010 ; Vol. 9, No. 6. pp. 1143-1155.
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AU - Vidalain, Pierre Olivier

AU - Senapedis, William

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AU - Barnekow, Angelika

AU - Rottapel, Robert

AU - Capellá, Gabriel

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