Structurally related TPR subunits contribute differently to the function of the anaphase-promoting complex in Drosophila melanogaster

Margit Pál, Olga Nagy, Dalma Ménesi, A. Udvardy, P. Deák

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The anaphase-promoting complex/cyclosome or APC/C is a key regulator of chromosome segregation and mitotic exit in eukaryotes. It contains at least 11 subunits, most of which are evolutionarily conserved. The most abundant constituents of the vertebrate APC/C are the four structurally related tetratrico-peptide repeat (TPR) subunits, the functions of which are not yet precisely understood. Orthologues of three of the TPR subunits have been identified in Drosophila. We have shown previously that one of the TPR subunits of the Drosophila APC/C, Apc3 (also known as Cdc27 or Mákos), is essential for development, and perturbation of its function results in mitotic cyclin accumulation and metaphase-like arrest. In this study we demonstrate that the Drosophila APC/C associates with a new TPR protein, a genuine orthologue of the vertebrate Apc7 subunit that is not found in yeasts. In addition to this, transgenic flies knocked down for three of the TPR genes Apc6 (Cdc16), Apc7 and Apc8 (Cdc23), by RNA interference were established to investigate their function. Whole-body expression of subunit-specific dsRNA efficiently silences these genes resulting in only residual mRNA concentrations. Apc6/Cdc16 and Apc8/Cdc23 silencing induces developmental delay and causes different pupal lethality. Cytological examination showed that these animals had an elevated level of apoptosis, high mitotic index and delayed or blocked mitosis in a prometaphase-metaphase-like state with overcondensed chromosomes. The arrested neuroblasts contained elevated levels of cyclin B but, surprisingly, cyclin A appeared to be degraded normally. Contrary to the situation for the Apc6/Cdc16 and Apc8/Cdc23 genes, the apparent loss of Apc7 function does not lead to the above abnormalities. Instead, the Apc7 knocked down animals and null mutants are viable and fertile, although they display mild chromosome segregation defects and anaphase delay. Nevertheless, the Apc7 subunit shows synergistic genetic interaction with Apc8/Cdc23 that, together with the phenotypic data, assumes a limited functional role for Apc7. Taken together, these data suggest that the structurally related TPR subunits contribute differently to the function of the anaphase-promoting complex.

Original languageEnglish
Pages (from-to)3238-3248
Number of pages11
JournalJournal of Cell Science
Volume120
Issue number18
DOIs
Publication statusPublished - Sep 15 2007

Fingerprint

Anaphase-Promoting Complex-Cyclosome
Drosophila melanogaster
Peptides
Drosophila
Chromosome Segregation
Metaphase
Vertebrates
Prometaphase
Genes
Cyclin B
Cyclin A
Anaphase
Mitotic Index
Cyclins
RNA Interference
Eukaryota
Mitosis
Diptera
Chromosomes
Yeasts

Keywords

  • APC/C
  • Apc6 (Cdc16)
  • Apc7
  • Apc8 (Cdc23)
  • TPR subunits
  • Transgenic RNAi

ASJC Scopus subject areas

  • Cell Biology

Cite this

Structurally related TPR subunits contribute differently to the function of the anaphase-promoting complex in Drosophila melanogaster. / Pál, Margit; Nagy, Olga; Ménesi, Dalma; Udvardy, A.; Deák, P.

In: Journal of Cell Science, Vol. 120, No. 18, 15.09.2007, p. 3238-3248.

Research output: Contribution to journalArticle

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