CAML loss causes anaphase failure and chromosome missegregation.
Cell Cycle
; 8(6): 940-9, 2009 Mar 15.
Article
en En
| MEDLINE
| ID: mdl-19229138
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Segregación Cromosómica
/
Inestabilidad Cromosómica
/
Proteínas Adaptadoras Transductoras de Señales
/
Anafase
/
Huso Acromático
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Cell Cycle
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos