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

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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, ... continued below

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Spence, Jeffrey R.; Go, Minjoung M.; Bahmanyar, S.; Barth,A.I.M. & Krauss, Sharon Wald March 17, 2006.

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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.

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  • Journal Name: Molecular and Cellular Biology; Journal Volume: 28; Journal Issue: 7; Related Information: Journal Publication Date: 2008

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  • Report No.: LBNL--59877
  • Grant Number: DE-AC02-05CH11231
  • Grant Number: NIHDK 059079, DK3232094
  • Grant Number: DOEBC032806
  • Office of Scientific & Technical Information Report Number: 929752
  • Archival Resource Key: ark:/67531/metadc897665

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Reports, articles and other documents harvested from the Office of Scientific and Technical Information.

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  • March 17, 2006

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  • Sept. 27, 2016, 1:39 a.m.

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  • Dec. 9, 2016, 9:18 p.m.

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Spence, Jeffrey R.; Go, Minjoung M.; Bahmanyar, S.; Barth,A.I.M. & Krauss, Sharon Wald. Downregulation of Protein 4.1R impairs centrosome function,bipolar spindle organization and anaphase, article, March 17, 2006; Berkeley, California. (digital.library.unt.edu/ark:/67531/metadc897665/: accessed November 18, 2017), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Government Documents Department.