Downregulation of Protein 4.1R impairs centrosome function,bipolar spindle organization and anaphase

Centrosomes nucleate and organize interphase MTs and areinstrumental in the assembly of the mitotic bipolar spindle. Here wereport that two members of the multifunctional protein 4.1 family havedistinct distributions at centrosomes. Protein 4.1R localizes to maturecentrioles whereas 4.1G is a compon...

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Bibliographic Details
Published in:Molecular and cellular biology 2006-03, Vol.28 (7)
Main Authors: Spence, Jeffrey R., Go, Minjoung M., Bahmanyar, S., Barth,A.I.M., Krauss, Sharon Wald
Format: Article
Language:English
Subjects:
59
ACCURACY
CHROMOSOMES
FASTENING
FOCUSING
FUNCTIONALS
MITOSIS
PROBES
protein 4.1 centrosomes mitotic spindles
PROTEINS
REGULATIONS
RNA
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Summary:Centrosomes nucleate and organize interphase MTs and areinstrumental in the assembly of the mitotic bipolar spindle. Here wereport that two members of the multifunctional protein 4.1 family havedistinct distributions at centrosomes. Protein 4.1R localizes to maturecentrioles whereas 4.1G is a component of the pericentriolar matrixsurrounding centrioles. To selectively probe 4.1R function, we used RNAinterference-mediated depletion of 4.1R without decreasing 4.1Gexpression. 4.1R downregulation reduces MT anchoring and organization atinterphase and impairs centrosome separation during prometaphase.Metaphase chromosomes fail to properly condense/align and spindleorganization is aberrant. Notably 4.1R depletion causes mislocalizationof its binding partner NuMA (Nuclear Mitotic Apparatus Protein),essential for spindle pole focusing, and disrupts ninein. Duringanaphase/telophase, 4.1R-depleted cells have lagging chromosomes andaberrant MT bridges. Our data provide functional evidence that 4.1R makescrucial contributions to centrosome integrity and to mitotic spindlestructure enabling mitosis and anaphase to proceed with the coordinatedprecision required to avoid pathological events.
ISSN:0270-7306
1098-5549