NDEL1 explained

Nuclear distribution protein nudE-like 1 is a protein that in humans is encoded by the NDEL1 gene.^{[1] [2] [3]}

It plays a significant role in intracellular transport and the process of cellular division via regulation of the dynein motor protein and its cofactor protein, Lis1.^[4] Ndel1 is a highly conserved protein and its human gene, NDEL1 is expressed in a wide variety of brain tissues which contributes to neuronal function and development.^{[5] [6] [7]} Nde1 and Ndel1 were in the past referred to as NudE and NudEL respectively.^{[8] [9]} The Nde1 protein is involved in nuclear migration throughout the process of neurogenesis.^[10] Studies have revealed that Ndel1 is structurally similar to Nde1 which both play a role in microtubule-based transport. Ndel1 and Nde1 are also thought to be associated with neurodevelopmental and psychiatric disorders.^[11] Secondary structure of Ndel1 is composed of various distinct domains: a C-terminal region, and a 200 amino acid N-terminal coiled-coil domain. The coiled-coil domain of Ndel1 serves as a self-associating stable parallel homodimer.^[12] Such structural components help with interactions between an array of binding partners, including the motor protein dynein and its cofactor protein, Lis1. Ndel1 forms a heterotetramer complex with Lis1 via the N-terminal coiled-coil domain. The Ndel1 N-terminal coiled-coil domain mediates binding to dynein, whereas the C-terminal domain interacts with Lis1, regulating the activity of the dynein complex.

This gene product is a thiol-activated oligopeptidase and is also known as Endooligopeptidase A in that context. It is phosphorylated in M phase of the cell cycle. Phosphorylation regulates the cell cycle-dependent distribution of this protein, with a fraction of the protein bound strongly to centrosomes in interphase and localized to mitotic spindles in early M phase. Overall, this protein plays a role in nervous system development. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

Other Interactions

NDEL1 has been shown to interact with Cyclin-dependent kinase 5, YWHAE,^[13] PAFAH1B1^{[1] [13]} and DISC1.^{[14] [15]}

Further reading

• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA . A "double adaptor" method for improved shotgun library construction . Analytical Biochemistry . 236 . 1 . 107–13 . Apr 1996 . 8619474 . 10.1006/abio.1996.0138 .
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA . Large-scale concatenation cDNA sequencing . Genome Research . 7 . 4 . 353–8 . Apr 1997 . 9110174 . 139146 . 10.1101/gr.7.4.353 .
• Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, Zago MA, Bordin S, Costa FF, Goldman GH, Carvalho AF, Matsukuma A, Baia GS, Simpson DH, Brunstein A, de Oliveira PS, Bucher P, Jongeneel CV, O'Hare MJ, Soares F, Brentani RR, Reis LF, de Souza SJ, Simpson AJ . Shotgun sequencing of the human transcriptome with ORF expressed sequence tags . Proceedings of the National Academy of Sciences of the United States of America . 97 . 7 . 3491–6 . Mar 2000 . 10737800 . 16267 . 10.1073/pnas.97.7.3491 . 2000PNAS...97.3491D . free .
• Feng Y, Olson EC, Stukenberg PT, Flanagan LA, Kirschner MW, Walsh CA . LIS1 regulates CNS lamination by interacting with mNudE, a central component of the centrosome . Neuron . 28 . 3 . 665–79 . Dec 2000 . 11163258 . 10.1016/S0896-6273(00)00145-8 . 15923472 . free .
• Ozeki Y, Tomoda T, Kleiderlein J, Kamiya A, Bord L, Fujii K, Okawa M, Yamada N, Hatten ME, Snyder SH, Ross CA, Sawa A . Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth . Proceedings of the National Academy of Sciences of the United States of America . 100 . 1 . 289–94 . Jan 2003 . 12506198 . 140954 . 10.1073/pnas.0136913100 . 2003PNAS..100..289O . free .
• Yan X, Li F, Liang Y, Shen Y, Zhao X, Huang Q, Zhu X . Human Nudel and NudE as regulators of cytoplasmic dynein in poleward protein transport along the mitotic spindle . Molecular and Cellular Biology . 23 . 4 . 1239–50 . Feb 2003 . 12556484 . 141156 . 10.1128/MCB.23.4.1239-1250.2003 .
• Cardoso C, Leventer RJ, Ward HL, Toyo-Oka K, Chung J, Gross A, Martin CL, Allanson J, Pilz DT, Olney AH, Mutchinick OM, Hirotsune S, Wynshaw-Boris A, Dobyns WB, Ledbetter DH . Refinement of a 400-kb critical region allows genotypic differentiation between isolated lissencephaly, Miller-Dieker syndrome, and other phenotypes secondary to deletions of 17p13.3 . American Journal of Human Genetics . 72 . 4 . 918–30 . Apr 2003 . 12621583 . 1180354 . 10.1086/374320 .
• 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 . Nature Genetics . 34 . 3 . 274–85 . Jul 2003 . 12796778 . 10.1038/ng1169 . 10301633 .
• Morris JA, Kandpal G, Ma L, Austin CP . DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation . Human Molecular Genetics . 12 . 13 . 1591–608 . Jul 2003 . 12812986 . 10.1093/hmg/ddg162 . free .
• Brandon NJ, Handford EJ, Schurov I, Rain JC, Pelling M, Duran-Jimeniz B, Camargo LM, Oliver KR, Beher D, Shearman MS, Whiting PJ . Disrupted in Schizophrenia 1 and Nudel form a neurodevelopmentally regulated protein complex: implications for schizophrenia and other major neurological disorders . Molecular and Cellular Neurosciences . 25 . 1 . 42–55 . Jan 2004 . 14962739 . 10.1016/j.mcn.2003.09.009 . 21261573 .
• Liang Y, Yu W, Li Y, Yang Z, Yan X, Huang Q, Zhu X . Nudel functions in membrane traffic mainly through association with Lis1 and cytoplasmic dynein . The Journal of Cell Biology . 164 . 4 . 557–66 . Feb 2004 . 14970193 . 2171987 . 10.1083/jcb.200308058 .
• Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S . Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions . Genome Research . 14 . 9 . 1711–8 . Sep 2004 . 15342556 . 515316 . 10.1101/gr.2435604 .
• Tarricone C, Perrina F, Monzani S, Massimiliano L, Kim MH, Derewenda ZS, Knapp S, Tsai LH, Musacchio A . Coupling PAF signaling to dynein regulation: structure of LIS1 in complex with PAF-acetylhydrolase . Neuron . 44 . 5 . 809–21 . Dec 2004 . 15572112 . 10.1016/j.neuron.2004.11.019 . free .
• Hayashi MA, Portaro FC, Bastos MF, Guerreiro JR, Oliveira V, Gorrão SS, Tambourgi DV, Sant'Anna OA, Whiting PJ, Camargo LM, Konno K, Brandon NJ, Camargo AC . Inhibition of NUDEL (nuclear distribution element-like)-oligopeptidase activity by disrupted-in-schizophrenia 1 . Proceedings of the National Academy of Sciences of the United States of America . 102 . 10 . 3828–33 . Mar 2005 . 15728732 . 553309 . 10.1073/pnas.0500330102 . 2005PNAS..102.3828H . free .
• Guerreiro JR, Winnischofer SM, Bastos MF, Portaro FC, Sogayar MC, de Camargo AC, Hayashi MA . Cloning and characterization of the human and rabbit NUDEL-oligopeptidase promoters and their negative regulation . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1730 . 1 . 77–84 . Jul 2005 . 16005531 . 10.1016/j.bbaexp.2005.06.001 .

Notes and References

1. Niethammer M, Smith DS, Ayala R, Peng J, Ko J, Lee MS, Morabito M, Tsai LH . NUDEL is a novel Cdk5 substrate that associates with LIS1 and cytoplasmic dynein . Neuron . 28 . 3 . 697–711 . Dec 2000 . 11163260 . 10.1016/S0896-6273(00)00147-1 . 11154069 . free .
2. Sasaki S, Shionoya A, Ishida M, Gambello MJ, Yingling J, Wynshaw-Boris A, Hirotsune S . A LIS1/NUDEL/cytoplasmic dynein heavy chain complex in the developing and adult nervous system . Neuron . 28 . 3 . 681–96 . Dec 2000 . 11163259 . 10.1016/S0896-6273(00)00146-X . 17738599 . free .
3. Web site: Entrez Gene: NDEL1 nudE nuclear distribution gene E homolog (A. nidulans)-like 1.
4. Garrott . Sharon R. . Gillies . John P. . Siva . Aravintha . Little . Saffron R. . El Jbeily . Rita . DeSantis . Morgan E. . June 2023 . Ndel1 disfavors dynein–dynactin–adaptor complex formation in two distinct ways . Journal of Biological Chemistry . 299 . 6 . 104735 . 10.1016/j.jbc.2023.104735 . free . 0021-9258 . 10248797 . 37086789.
5. Sasaki . Shinji . Mori . Daisuke . Toyo-oka . Kazuhito . Chen . Amy . Garrett-Beal . Lisa . Muramatsu . Masami . Miyagawa . Shuji . Hiraiwa . Noriko . Yoshiki . Atsushi . Wynshaw-Boris . Anthony . Hirotsune . Shinji . 2005-09-01 . Complete Loss of Ndel1 Results in Neuronal Migration Defects and Early Embryonic Lethality . Molecular and Cellular Biology . en . 25 . 17 . 7812–7827 . 10.1128/MCB.25.17.7812-7827.2005 . 1098-5549 . 1190282 . 16107726.
6. Shim . Su Yeon . Samuels . Benjamin Adam . Wang . Jian . Neumayer . Gernot . Belzil . Camille . Ayala . Ramses . Shi . Yang . Shi . Yujiang . Tsai . Li-Huei . Nguyen . Minh Dang . May 2008 . Ndel1 Controls the Dynein-mediated Transport of Vimentin during Neurite Outgrowth . Journal of Biological Chemistry . 283 . 18 . 12232–12240 . 10.1074/jbc.m710200200 . free . 18303022 . 0021-9258.
7. Shu . Tianzhi . Ayala . Ramses . Nguyen . Minh-Dang . Xie . Zhigang . Gleeson . Joseph G. . Tsai . Li-Huei . October 2004 . Ndel1 Operates in a Common Pathway with LIS1 and Cytoplasmic Dynein to Regulate Cortical Neuronal Positioning . Neuron . 44 . 2 . 263–277 . 10.1016/j.neuron.2004.09.030 . 15473966 . 0896-6273. free .
8. McKenney . Richard J. . Vershinin . Michael . Kunwar . Ambarish . Vallee . Richard B. . Gross . Steven P. . April 2010 . LIS1 and NudE Induce a Persistent Dynein Force-Producing State . Cell . 141 . 2 . 304–314 . 10.1016/j.cell.2010.02.035 . 0092-8674 . 2881166 . 20403325.
9. Żyłkiewicz . Eliza . Kijańska . Monika . Choi . Won-Chan . Derewenda . Urszula . Derewenda . Zygmunt S. . Stukenberg . P. Todd . 2011-01-31 . The N-terminal coiled-coil of Ndel1 is a regulated scaffold that recruits LIS1 to dynein . Journal of Cell Biology . 192 . 3 . 433–445 . 10.1083/jcb.201011142 . 1540-8140 . 3101096 . 21282465.
10. Soto-Perez . Jaseph . Baumgartner . Marybeth . Kanadia . Rahul N. . 2020 . Role of NDE1 in the Development and Evolution of the Gyrified Cortex . Frontiers in Neuroscience . 14 . 10.3389/fnins.2020.617513 . free . 1662-453X . 7775536 . 33390896.
11. Bradshaw . Nicholas J. . Hennah . William . Soares . Dinesh C. . 2013-10-01 . NDE1 and NDEL1: twin neurodevelopmental proteins with similar 'nature' but different 'nurture' . BioMolecular Concepts . en . 4 . 5 . 447–464 . 10.1515/bmc-2013-0023 . 1868-503X . 3787581 . 24093049.
12. Derewenda . Urszula . Tarricone . Cataldo . Choi . Won Chan . Cooper . David R. . Lukasik . Steve . Perrina . Franco . Tripathy . Ashutosh . Kim . Myung Hee . Cafiso . David S. . Musacchio . Andrea . Derewenda . Zygmunt S. . November 2007 . The Structure of the Coiled-Coil Domain of Ndel1 and the Basis of Its Interaction with Lis1, the Causal Protein of Miller-Dieker Lissencephaly . Structure . 15 . 11 . 1467–1481 . 10.1016/j.str.2007.09.015 . 17997972 . 0969-2126.
13. 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 . Nature Genetics . 34 . 3 . 274–85 . Jul 2003 . 12796778 . 10.1038/ng1169 . 10301633 .
14. Morris JA, Kandpal G, Ma L, Austin CP . DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation . Human Molecular Genetics . 12 . 13 . 1591–608 . Jul 2003 . 12812986 . 10.1093/hmg/ddg162 . free .
15. Ozeki Y, Tomoda T, Kleiderlein J, Kamiya A, Bord L, Fujii K, Okawa M, Yamada N, Hatten ME, Snyder SH, Ross CA, Sawa A . Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth . Proceedings of the National Academy of Sciences of the United States of America . 100 . 1 . 289–94 . Jan 2003 . 12506198 . 140954 . 10.1073/pnas.0136913100 . 2003PNAS..100..289O . free .