CAML loss causes anaphase failure and chromosome missegregation

Yu Liu, Liviu Malureanu, Karthik B. Jeganathan, David Dinh Tran, Lonn D. Lindquist, Jan M. Van Deursen, Richard J. Bram

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Calcium modulating cyclophilin ligand (CAML) is a ubiquitously expressed cytoplasmic protein that is implicated in the EGFR and LCK signaling pathways and required for early embryonic and thymocyte development. To further define the critical biological functions of CAML at the cellular level, we generated CAML-deleted mouse embryonic fibroblasts (MEFs) using an in vitro Cre-loxP mediated conditional knockout system. We found that CAML-/- MEFs have severely impaired proliferation and a strong reduction of normal anaphases. The primary mitotic defect of CAML-/- MEFs is that duplicated chromosomes fail to segregate in anaphase, resulting in nuclear bisection by the cleavage furrow as cells decondense their DNA and exit mitosis, highly reminiscent of the "cut" phenotype in fission yeast. This phenotype is due to spindle dysfunction rather than inability to resolve physical connections between sister chromatids. Furthermore, CAML-/- MEFs display defects often seen in cells with mitotic checkpoint gene deficiencies, including lagging and misaligned chromosomes and chromatin bridges. Consistent with this, we found that CAML-/- MEFs have a modestly weakened spindle assembly checkpoint (SAC) and increased aneuploidy. Thus, our data identify CAML as a novel chromosomal instability gene and suggest that CAML protein acts as a key regulator of mitotic spindle function and a modulator of SAC maintenance.

Original languageEnglish (US)
Pages (from-to)940-949
Number of pages10
JournalCell Cycle
Volume8
Issue number6
DOIs
StatePublished - Mar 15 2009

Keywords

  • Aneuploidy
  • CAML
  • Chromosome segregation
  • Cut phenotype
  • Mitosis
  • Spindle assembly checkpoint

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Liu, Y., Malureanu, L., Jeganathan, K. B., Tran, D. D., Lindquist, L. D., Van Deursen, J. M., & Bram, R. J. (2009). CAML loss causes anaphase failure and chromosome missegregation. Cell Cycle, 8(6), 940-949. https://doi.org/10.4161/cc.8.6.7948