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Nuclear mitotic apparatus protein 1

Definition:

Microtubule (MT)-binding protein that plays a role in the formation and maintenance of the spindle poles and the alignement and the segregation of chromosomes during mitotic cell division. Functions to tether the minus ends of MTs at the spindle poles, which is critical for the establishment and maintenance of the spindle poles. Plays a role in the establishment of the mitotic spindle orientation during metaphase and elongation during anaphase in a dynein-dynactin-dependent manner. In metaphase, part of a ternary complex composed of GPSM2 and G(i) alpha proteins, that regulates the recruitment and anchorage of the dynein-dynactin complex in the mitotic cell cortex regions situated above the two spindle poles, and hence regulates the correct oritentation of the mitotic spindle. During anaphase, mediates the recruitment and accumulation of the dynein-dynactin complex at the cell membrane of the polar cortical region through direct association with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), and hence participates in the regulation of the spindle elongation and chromosome segregation. Binds also to other polyanionic phosphoinositides, such as phosphatidylinositol 3-phosphate (PIP), lysophosphatidic acid (LPA) and phosphatidylinositol triphosphate (PIP3), in vitro. Also required for proper orientation of the mitotic spindle during asymmetric cell divisions. Plays a role in mitotic MT aster assembly. Involved in anastral spindle assembly. Positively regulates TNKS protein localization to spindle poles in mitosis. Highly abundant component of the nuclear matrix where it may serve a non-mitotic structural role, occupies the majority of the nuclear volume. Required for epidermal differentiation and hair follicle morphogenesis (By similarity).

References:

[1]. M V Nachury, et al. Importin beta is a mitotic target of the small GTPase Ran in spindle assembly. Cell. 2001 Jan 12;104(1):95-106. [Content Brief]

[2]. Sachin Kotak, et al. Cortical dynein is critical for proper spindle positioning in human cells. J Cell Biol. 2012 Oct 1;199(1):97-110. [Content Brief]

[3]. C Wiese, et al. Role of importin-beta in coupling Ran to downstream targets in microtubule assembly. Science. 2001 Jan 26;291(5504):653-6. [Content Brief]

[4]. J Harborth, et al. Self assembly of NuMA: multiarm oligomers as structural units of a nuclear lattice. EMBO J. 1999 Mar 15;18(6):1689-700. [Content Brief]

[5]. William Chang, et al. NuMA is a major acceptor of poly(ADP-ribosyl)ation by tankyrase 1 in mitosis. Biochem J. 2005 Oct 15;391(Pt 2):177-84. [Content Brief]

[6]. Alain D Silk, et al. Requirements for NuMA in maintenance and establishment of mammalian spindle poles. J Cell Biol. 2009 Mar 9;184(5):677-90. [Content Brief]

[7]. Shinya Ohta, et al. CENP-32 is required to maintain centrosomal dominance in bipolar spindle assembly. Mol Biol Cell. 2015 Apr 1;26(7):1225-37. [Content Brief]

[8]. Sachin Kotak, et al. NuMA phosphorylation by CDK1 couples mitotic progression with cortical dynein function. EMBO J. 2013 Sep 11;32(18):2517-29. [Content Brief]

[9]. Richard W Wong, et al. Rae1 interaction with NuMA is required for bipolar spindle formation. Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19783-7. [Content Brief]

[10]. Sachin Kotak, et al. NuMA interacts with phosphoinositides and links the mitotic spindle with the plasma membrane. EMBO J. 2014 Aug 18;33(16):1815-30. [Content Brief]

[11]. Tomomi Kiyomitsu, et al. Cortical dynein and asymmetric membrane elongation coordinately position the spindle in anaphase. Cell. 2013 Jul 18;154(2):391-402. [Content Brief]

[12]. Xiaogang Chu, et al. Nuclear Mitotic Apparatus (NuMA) Interacts with and Regulates Astrin at the Mitotic Spindle. J Biol Chem. 2016 Sep 16;291(38):20055-67. [Content Brief]

[13]. Zhen Zheng, et al. Cell cycle-regulated membrane binding of NuMA contributes to efficient anaphase chromosome separation. Mol Biol Cell. 2014 Mar;25(5):606-19. [Content Brief]

[14]. Lindsey Seldin, et al. NuMA localization, stability, and function in spindle orientation involve 4.1 and Cdk1 interactions. Mol Biol Cell. 2013 Dec;24(23):3651-62. [Content Brief]

[15]. Kaowen Yan, et al. The deubiquitinating enzyme complex BRISC is required for proper mitotic spindle assembly in mammalian cells. J Cell Biol. 2015 Jul 20;210(2):209-24. [Content Brief]

[16]. Lindsey Seldin, et al. NuMA-microtubule interactions are critical for spindle orientation and the morphogenesis of diverse epidermal structures. Elife. 2016 Jan 14;5:e12504. [Content Brief]

[17]. Tomomi Kiyomitsu, et al. Chromosome- and spindle-pole-derived signals generate an intrinsic code for spindle position and orientation. Nat Cell Biol. 2012 Feb 12;14(3):311-7. [Content Brief]

[18]. Quansheng Du, et al. LGN blocks the ability of NuMA to bind and stabilize microtubules. A mechanism for mitotic spindle assembly regulation. Curr Biol. 2002 Nov 19;12(22):1928-33. [Content Brief]

[19]. D A Compton, et al. Mutation of the predicted p34cdc2 phosphorylation sites in NuMA impair the assembly of the mitotic spindle and block mitosis. J Cell Sci. 1995 Feb;108 ( Pt 2):621-33. [Content Brief]

[20]. Laurence Haren, et al. Direct binding of NuMA to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules. J Cell Sci. 2002 May 1;115(Pt 9):1815-24. [Content Brief]

[21]. Jinwei Zhu, et al. LGN/mInsc and LGN/NuMA complex structures suggest distinct functions in asymmetric cell division for the Par3/mInsc/LGN and Gαi/LGN/NuMA pathways. Mol Cell. 2011 Aug 5;43(3):418-31. [Content Brief]

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