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 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.
- Research Organization:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- USDOE; Department of Defense BC032806, National Institutesof Health DK059079
- DOE Contract Number:
- DE-AC02-05CH11231; NIHDK 059079, DK3232094; DOEBC032806
- OSTI ID:
- 929752
- Report Number(s):
- LBNL-59877; MCEBD4; R&D Project: 863L1A, LO178, LO310; TRN: US200812%%643
- Journal Information:
- Molecular and Cellular Biology, Vol. 28, Issue 7; Related Information: Journal Publication Date: 2008; ISSN 0270-7306
- Country of Publication:
- United States
- Language:
- English
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