The nuclear-mitotic apparatus protein is important in the establishment and maintenance of the bipolar mitotic spindle apparatus

CH Yang and M Snyder

Department of Biology, Yale University, New Haven, Connecticut 06511.

The formation and maintenance of the bipolar mitotic spindle apparatus require a complex and balanced interplay of several mechanisms, including the stabilization and separation of polar microtubules and the action of various microtubule motors. Nonmicrotubule elements are also present throughout the spindle apparatus and have been proposed to provide a structural support for the spindle. The Nuclear-Mitotic Apparatus protein (NuMA) is an abundant 240 kD protein that is present in the nucleus of interphase cells and concentrates in the polar regions of the spindle apparatus during mitosis. Sequence analysis indicates that NuMA possesses an unusually long alpha-helical central region characteristic of many filament forming proteins. In this report we demonstrate that microinjection of anti-NuMA antibodies into interphase and prophase cells results in a failure to form a mitotic spindle apparatus. Furthermore, injection of metaphase cells results in the collapse of the spindle apparatus into a monopolar microtubule array. These results identify for the first time a nontubulin component important for both the establishment and stabilization of the mitotic spindle apparatus in multicellular organisms. We suggest that nonmicrotubule structural components may be important for these processes.

Volume 3, Issue 11, pp. 1259-1267, 11/01/1992
Copyright © 1992 by The American Society for Cell Biology

This article has been cited by other articles:

				H. Si, S. C. Verma, M. A. Lampson, Q. Cai, and E. S. Robertson Kaposi's Sarcoma-Associated Herpesvirus-Encoded LANA Can Interact with the Nuclear Mitotic Apparatus Protein To Regulate Genome Maintenance and Segregation J. Virol., July 1, 2008; 82(13): 6734 - 6746. [Abstract] [Full Text] [PDF]

				S. W. Krauss, J. R. Spence, S. Bahmanyar, A. I. M. Barth, M. M. Go, D. Czerwinski, and A. J. Meyer Downregulation of Protein 4.1R, a Mature Centriole Protein, Disrupts Centrosomes, Alters Cell Cycle Progression, and Perturbs Mitotic Spindles and Anaphase Mol. Cell. Biol., April 1, 2008; 28(7): 2283 - 2294. [Abstract] [Full Text] [PDF]

				L.-Y. Yan, J.-C. Huang, Z.-Y. Zhu, Z.-L. Lei, L.-H. Shi, C.-L. Nan, Z.-J. Zhao, Y.-C. OuYang, X.-F. Song, Q.-Y. Sun, et al. NuMA distribution and microtubule configuration in rabbit oocytes and cloned embryos. Reproduction, December 1, 2006; 132(6): 869 - 876. [Abstract] [Full Text] [PDF]

				N. Van Thuan, S. Wakayama, S. Kishigami, and T. Wakayama Donor Centrosome Regulation of Initial Spindle Formation in Mouse Somatic Cell Nuclear Transfer: Roles of Gamma-Tubulin and Nuclear Mitotic Apparatus Protein 1 Biol Reprod, May 1, 2006; 74(5): 777 - 787. [Abstract] [Full Text] [PDF]

				S. Kammerer, R. B. Roth, C. R. Hoyal, R. Reneland, G. Marnellos, M. Kiechle, U. Schwarz-Boeger, L. R. Griffiths, F. Ebner, J. Rehbock, et al. Association of the NuMA region on chromosome 11q13 with breast cancer susceptibility PNAS, February 8, 2005; 102(6): 2004 - 2009. [Abstract] [Full Text] [PDF]

				S.-C. Ng, N. Chen, W.-Y. Yip, S.-L. Liow, G.-Q. Tong, B. Martelli, L. G. Tan, and P. Martelli The first cell cycle after transfer of somatic cell nuclei in a non-human primate Development, May 15, 2004; 131(10): 2475 - 2484. [Abstract] [Full Text] [PDF]

				P. Taimen and M. Kallajoki NuMA and nuclear lamins behave differently in Fas-mediated apoptosis J. Cell Sci., February 1, 2003; 116(3): 571 - 583. [Abstract] [Full Text] [PDF]

				M. B. Gordon, L. Howard, and D. A. Compton Chromosome Movement in Mitosis Requires Microtubule Anchorage at Spindle Poles J. Cell Biol., January 29, 2001; 152(3): 425 - 434. [Abstract] [Full Text] [PDF]

				Y. Takai, T. Sasaki, and T. Matozaki Small GTP-Binding Proteins Physiol Rev, January 1, 2001; 81(1): 153 - 208. [Abstract] [Full Text] [PDF]

				D. L. Walker, D. Wang, Y. Jin, U. Rath, Y. Wang, J. Johansen, and K. M. Johansen Skeletor, a Novel Chromosomal Protein That Redistributes during Mitosis Provides Evidence for the Formation of a Spindle Matrix J. Cell Biol., December 18, 2000; 151(7): 1401 - 1412. [Abstract] [Full Text] [PDF]

				W. S. Saunders, M. Shuster, X. Huang, B. Gharaibeh, A. H. Enyenihi, I. Petersen, and S. M. Gollin Chromosomal instability and cytoskeletal defects in oral cancer cells PNAS, January 4, 2000; 97(1): 303 - 308. [Abstract] [Full Text] [PDF]

				S Sazer and M Dasso The ran decathlon: multiple roles of Ran J. Cell Sci., January 4, 2000; 113(7): 1111 - 1118. [Abstract] [PDF]

				K. Ye, D. A. Compton, M. M. Lai, L. D. Walensky, and S. H. Snyder Protein 4.1N Binding to Nuclear Mitotic Apparatus Protein in PC12 Cells Mediates the Antiproliferative Actions of Nerve Growth Factor J. Neurosci., December 15, 1999; 19(24): 10747 - 10756. [Abstract] [Full Text] [PDF]

				J. A. Kahana and D. W. Cleveland Beyond Nuclear Transport: Ran-GTP as a Determinant of Spindle Assembly J. Cell Biol., September 20, 1999; 146(6): 1205 - 1210. [Abstract] [Full Text] [PDF]

				F. Gindullis and I. Meier Matrix Attachment Region Binding Protein MFP1 Is Localized in Discrete Domains at the Nuclear Envelope PLANT CELL, June 1, 1999; 11(6): 1117 - 1128. [Abstract] [Full Text]

				A. Melnick and J. D. Licht Deconstructing a Disease: RAR{alpha}, Its Fusion Partners, and Their Roles in the Pathogenesis of Acute Promyelocytic Leukemia Blood, May 15, 1999; 93(10): 3167 - 3215. [Full Text] [PDF]

				S. N. Mattagajasingh, S.-C. Huang, J. S. Hartenstein, M. Snyder, V. T. Marchesi, and E. J. Benz Jr. A Nonerythroid Isoform of Protein 4.1R Interacts with the Nuclear Mitotic Apparatus (NuMA) Protein J. Cell Biol., April 5, 1999; 145(1): 29 - 43. [Abstract] [Full Text] [PDF]

				O. Zatsepina, A Rousselet, P. Chan, M. Olson, E. Jordan, and M Bornens The nucleolar phosphoprotein B23 redistributes in part to the spindle poles during mitosis J. Cell Sci., January 2, 1999; 112(4): 455 - 466. [Abstract] [PDF]

				M. Esteban, G Giovinazzo, A de la Hera, and C Goday PUMA1: a novel protein that associates with the centrosomes, spindle and centromeres in the nematode Parascaris J. Cell Sci., January 3, 1998; 111(6): 723 - 735. [Abstract] [PDF]

				A Merdes and D. Cleveland The role of NuMA in the interphase nucleus J. Cell Sci., January 1, 1998; 111(1): 71 - 79. [Abstract] [PDF]

				R. Heald, R. Tournebize, A. Habermann, E. Karsenti, and A. Hyman Spindle Assembly in Xenopus Egg Extracts: Respective Roles of Centrosomes and Microtubule Self-Organization J. Cell Biol., August 11, 1997; 138(3): 615 - 628. [Abstract] [Full Text] [PDF]

				A Saredi, L Howard, and D. Compton Phosphorylation regulates the assembly of NuMA in a mammalian mitotic extract J. Cell Sci., January 6, 1997; 110(11): 1287 - 1297. [Abstract] [PDF]

				A. Saredi, L. Howard, and D. A. Compton NuMA assembles into an extensive filamentous structure when expressed in the cell cytoplasm J. Cell Sci., March 1, 1996; 109(3): 619 - 630. [Abstract] [PDF]

				H. Hsu and N. Yeh Dynamic changes of NuMA during the cell cycle and possible appearance of a truncated form of NuMA during apoptosis J. Cell Sci., January 2, 1996; 109(2): 277 - 288. [Abstract] [PDF]

				W. Whitfield, M. Chaplin, K Oegema, H Parry, and D. Glover The 190 kDa centrosome-associated protein of Drosophila melanogaster contains four zinc finger motifs and binds to specific sites on polytene chromosomes J. Cell Sci., January 11, 1995; 108(11): 3377 - 3387. [Abstract] [PDF]

				C. Sparks, E. Fey, C. Vidair, and S. Doxsey Phosphorylation of NUMA occurs during nuclear breakdown and not mitotic spindle assembly J. Cell Sci., January 11, 1995; 108(11): 3389 - 3396. [Abstract] [PDF]

				D. Compton and C Luo Mutation of the predicted p34cdc2 phosphorylation sites in NuMA impair the assembly of the mitotic spindle and block mitosis J. Cell Sci., January 2, 1995; 108(2): 621 - 633. [Abstract] [PDF]

				T. Tang, C. Tang, Y. Chao, and C. Wu Nuclear mitotic apparatus protein (NuMA): spindle association, nuclear targeting and differential subcellular localization of various NuMA isoforms J. Cell Sci., January 6, 1994; 107(6): 1389 - 1402. [Abstract] [PDF]

				J. Harborth, K. Weber, and M. Osborn GAS41, a Highly Conserved Protein in Eukaryotic Nuclei, Binds to NuMA J. Biol. Chem., October 6, 2000; 275(41): 31979 - 31985. [Abstract] [Full Text] [PDF]