5yi4

Structural highlights

Function

NDEL1_MOUSE Required for organization of the cellular microtubule array and microtubule anchoring at the centrosome. May regulate microtubule organization at least in part by targeting the microtubule severing protein KATNA1 to the centrosome. Also positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus ends. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the centripetal motion of secretory vesicles and the coupling of the nucleus and centrosome. Also required during brain development for the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate. Plays a role, together with DISC1, in the regulation of neurite outgrowth. Required for mitosis in some cell types but appears to be dispensible for mitosis in cortical neuronal progenitors, which instead requires NDE1. Facilitates the polymerization of neurofilaments from the individual subunits NEFH and NEFL. Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts (PubMed:27777970).^{[1] [2] [3] [4] [5] [6]} DISC1_MOUSE Involved in the regulation of multiple aspects of embryonic and adult neurogenesis. Required for neural progenitor proliferation in the ventrical/subventrical zone during embryonic brain development and in the adult dentate gyrus of the hippocampus. Participates in the Wnt-mediated neural progenitor proliferation as a positive regulator by modulating GSK3B activity and CTNNB1 abundance. Plays a role as a modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including neuron positioning, dendritic development and synapse formation. Inhibits the activation of AKT-mTOR signaling upon interaction with CCDC88A. Regulates the migration of early-born granule cell precursors toward the dentate gyrus during the hippocampal development. Plays a role, together with PCNT, in the microtubule network formation.^{[7] [8] [9] [10]}

References

1. ↑ Toyo-oka K, Shionoya A, Gambello MJ, Cardoso C, Leventer R, Ward HL, Ayala R, Tsai LH, Dobyns W, Ledbetter D, Hirotsune S, Wynshaw-Boris A. 14-3-3epsilon is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome. Nat Genet. 2003 Jul;34(3):274-85. PMID:12796778 doi:http://dx.doi.org/10.1038/ng1169
2. ↑ Nguyen MD, Shu T, Sanada K, Lariviere RC, Tseng HC, Park SK, Julien JP, Tsai LH. A NUDEL-dependent mechanism of neurofilament assembly regulates the integrity of CNS neurons. Nat Cell Biol. 2004 Jul;6(7):595-608. doi: 10.1038/ncb1139. Epub 2004 Jun 20. PMID:15208636 doi:http://dx.doi.org/10.1038/ncb1139
3. ↑ Shu T, Ayala R, Nguyen MD, Xie Z, Gleeson JG, Tsai LH. Ndel1 operates in a common pathway with LIS1 and cytoplasmic dynein to regulate cortical neuronal positioning. Neuron. 2004 Oct 14;44(2):263-77. doi: 10.1016/j.neuron.2004.09.030. PMID:15473966 doi:http://dx.doi.org/10.1016/j.neuron.2004.09.030
4. ↑ Sasaki S, Mori D, Toyo-oka K, Chen A, Garrett-Beal L, Muramatsu M, Miyagawa S, Hiraiwa N, Yoshiki A, Wynshaw-Boris A, Hirotsune S. Complete loss of Ndel1 results in neuronal migration defects and early embryonic lethality. Mol Cell Biol. 2005 Sep;25(17):7812-27. doi: 10.1128/MCB.25.17.7812-7827.2005. PMID:16107726 doi:http://dx.doi.org/10.1128/MCB.25.17.7812-7827.2005
5. ↑ Toyo-Oka K, Sasaki S, Yano Y, Mori D, Kobayashi T, Toyoshima YY, Tokuoka SM, Ishii S, Shimizu T, Muramatsu M, Hiraiwa N, Yoshiki A, Wynshaw-Boris A, Hirotsune S. Recruitment of katanin p60 by phosphorylated NDEL1, an LIS1 interacting protein, is essential for mitotic cell division and neuronal migration. Hum Mol Genet. 2005 Nov 1;14(21):3113-28. Epub 2005 Oct 3. PMID:16203747 doi:http://dx.doi.org/ddi339
6. ↑ Fujiwara T, Ye S, Castro-Gomes T, Winchell CG, Andrews NW, Voth DE, Varughese KI, Mackintosh SG, Feng Y, Pavlos N, Nakamura T, Manolagas SC, Zhao H. PLEKHM1/DEF8/RAB7 complex regulates lysosome positioning and bone homeostasis. JCI Insight. 2016 Oct 20;1(17):e86330. doi: 10.1172/jci.insight.86330. PMID:27777970 doi:http://dx.doi.org/10.1172/jci.insight.86330
7. ↑ Duan X, Chang JH, Ge S, Faulkner RL, Kim JY, Kitabatake Y, Liu XB, Yang CH, Jordan JD, Ma DK, Liu CY, Ganesan S, Cheng HJ, Ming GL, Lu B, Song H. Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain. Cell. 2007 Sep 21;130(6):1146-58. Epub 2007 Sep 6. PMID:17825401 doi:http://dx.doi.org/10.1016/j.cell.2007.07.010
8. ↑ Mao Y, Ge X, Frank CL, Madison JM, Koehler AN, Doud MK, Tassa C, Berry EM, Soda T, Singh KK, Biechele T, Petryshen TL, Moon RT, Haggarty SJ, Tsai LH. Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3beta/beta-catenin signaling. Cell. 2009 Mar 20;136(6):1017-31. doi: 10.1016/j.cell.2008.12.044. PMID:19303846 doi:http://dx.doi.org/10.1016/j.cell.2008.12.044
9. ↑ Meyer KD, Morris JA. Disc1 regulates granule cell migration in the developing hippocampus. Hum Mol Genet. 2009 Sep 1;18(17):3286-97. doi: 10.1093/hmg/ddp266. Epub 2009 Jun , 5. PMID:19502360 doi:http://dx.doi.org/10.1093/hmg/ddp266
10. ↑ Kim JY, Duan X, Liu CY, Jang MH, Guo JU, Pow-anpongkul N, Kang E, Song H, Ming GL. DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212. Neuron. 2009 Sep 24;63(6):761-73. doi: 10.1016/j.neuron.2009.08.008. PMID:19778506 doi:http://dx.doi.org/10.1016/j.neuron.2009.08.008
11. ↑ Ye F, Kang E, Yu C, Qian X, Jacob F, Yu C, Mao M, Poon RYC, Kim J, Song H, Ming GL, Zhang M. DISC1 Regulates Neurogenesis via Modulating Kinetochore Attachment of Ndel1/Nde1 during Mitosis. Neuron. 2017 Dec 6;96(5):1041-1054.e5. doi: 10.1016/j.neuron.2017.10.010. Epub, 2017 Nov 2. PMID:29103808 doi:http://dx.doi.org/10.1016/j.neuron.2017.10.010