Mutations in the HECT domain of NEDD4L lead to AKT-mTOR pathway deregulation and cause periventricular nodular heterotopia

Nature Genetics

Volumn 48, Issue 11, 2016, Pages 1349-1358

  Broix, Loïc ^a,b,c,d,e   Jagline, Hélène ^a,b,c,d   Ivanova, Ekaterina L ^a,b,c,d   Schmucker, Stéphane ^a,b,c,d   Drouot, Nathalie ^a,b,c,d   Clayton Smith, Jill ^f   Pagnamenta, Alistair T ^g   Metcalfe, Kay A ^f   Isidor, Bertrand ^h   Louvier, Ulrike Walther ⁱ   Poduri, Annapurna ^j   Taylor, Jenny C ^g   Tilly, Peggy ^a,b,c,d   Poirier, Karine ^e   Saillour, Yoann ^e   Lebrun, Nicolas ^e   Stemmelen, Tristan ^a,b,c,d   Rudolf, Gabrielle ^a,b,c,d   Muraca, Giuseppe ^e   Saintpierre, Benjamin ^e   Elmorjani, Adrienne ^e   Moïse, Martin ^k   Weirauch, Nathalie Bednarek ^l   Guerrini, Renzo ^m   Boland, Anne ⁿ   Olaso, Robert ⁿ   Masson, Cecile ^o   Tripathy, Ratna ^p   Keays, David ^p   Beldjord, Cherif ^q   Nguyen, Laurent ^k   Godin, Juliette ^a,b,c,d   Kini, Usha ^r   Nischké, Patrick ^o   Deleuze, Jean François ⁿ   Bahi Buisson, Nadia ^o   Sumara, Izabela ^a,b,c,d   Hinckelmann, Maria Victoria ^a,b,c,d   Chelly, Jamel ^a,b,c,d,s   more..

^a INSTITUT DE GÉNÉTIQUE ET DE BIOLOGIE MOLÉCULAIRE ET CELLULAIRE   (France)

^b CNRS U7104   (France)

^c INSERM   (France)

^d UNIVERSITÉ DE STRASBOURG   (France)

^e INSTITUT COCHIN   (France)

^f MANCHESTER UNIVERSITY NHS FOUNDATION TRUST   (United Kingdom)

^g UNIVERSITY OF OXFORD   (United Kingdom)

^h NANTES UNIVERSITY HOSPITAL   (France)

ⁱ MONTPELLIER UNIVERSITY HOSPITAL   (France)

^j BOSTON CHILDREN S HOSPITAL   (United States)

^k UNIVERSITY OF LIÈGE   (Belgium)

^l HÔPITAL MAISON BLANCHE   (France)

^m UNIVERSITY OF FLORENCE   (Italy)

ⁿ DIF   (France)

^o IMAGINE INSTITUTE   (France)

^p RESEARCH INSTITUTE OF MOLECULAR PATHOLOGY   (Austria)

^q Oxford University Hospitals NHS Trust ^*  (France)

^r OXFORD UNIVERSITY HOSPITALS NHS FOUNDATION TRUST   (United Kingdom)

^s HÔPITAL CIVIL   (France)

more..

Author keywords

[No Author keywords available]

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN; PROTEASOME; PROTEIN KINASE B; UBIQUITIN PROTEIN LIGASE; UBIQUITIN PROTEIN LIGASE NEDD4 L; UNCLASSIFIED DRUG; ESCRT PROTEIN; MTOR PROTEIN, HUMAN; NEDD4 UBIQUITIN PROTEIN LIGASES; TARGET OF RAPAMYCIN KINASE; UBIQUITIN;

ANIMAL TISSUE; ARTICLE; CHILD; CLEFT PALATE; CONTROLLED STUDY; ELECTROPORATION; EMBRYO; EXOME; FEMALE; HUMAN; HUMAN CELL; IMMUNOBLOTTING; IMMUNOFLUORESCENCE; IN SITU HYBRIDIZATION; IN VITRO STUDY; INFANT; MALE; MISSENSE MUTATION; MOUSE; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; PERIVENTRICULAR HETEROTOPIA; PRESCHOOL CHILD; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; SCHOOL CHILD; SEQUENCE ANALYSIS; SYNDACTYLY; UBIQUITINATION; WILD TYPE; ANIMAL; CELL CULTURE; GENETICS; METABOLISM; PROTEIN DOMAIN; SIGNAL TRANSDUCTION;

ANIMALS; CELLS, CULTURED; ENDOSOMAL SORTING COMPLEXES REQUIRED FOR TRANSPORT; FEMALE; HUMANS; MALE; MICE; MUTATION, MISSENSE; PERIVENTRICULAR NODULAR HETEROTOPIA; PROTEIN DOMAINS; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; UBIQUITIN; UBIQUITIN-PROTEIN LIGASES;

EID: 84989927586     PISSN: 10614036     EISSN: 15461718     Source Type: Journal    
DOI: 10.1038/ng.3676     Document Type: Article

References (40)

1. Caviness, V.S. Jr., Takahashi, T. & Nowakowski, R.S. Numbers, time and neocortical neuronogenesis: a general developmental and evolutionary model. Trends Neurosci. 18, 379-383 (1995).
2. Rakic, P. & Caviness, V.S. Jr. Cortical development: view from neurological mutants two decades later. Neuron 14, 1101-1104 (1995).
3. Barkovich, A.J., Guerrini, R., Kuzniecky, R.I., Jackson, G.D. & Dobyns, W.B. A developmental and genetic classifcation for malformations of cortical development: update 2012. Brain 135, 1348-1369 (2012).
4. Francis, F. et al. Human disorders of cortical development: from past to present. Eur. J. Neurosci. 23, 877-893 (2006).
5. Guerrini, R. & Dobyns, W.B. Malformations of cortical development: clinical features and genetic causes. Lancet Neurol. 13, 710-726 (2014).
6. Fox, J.W. et al. Mutations in flamin 1 prevent migration of cerebral cortical neurons in human periventricular heterotopia. Neuron 21, 1315-1325 (1998).
7. Parrini, E. et al. Periventricular heterotopia: phenotypic heterogeneity and correlation with flamin A mutations. Brain 129, 1892-1906 (2006).
8. Ferland, R.J. et al. Disruption of neural progenitors along the ventricular and subventricular zones in periventricular heterotopia. Hum. Mol. Genet. 18, 497-516 (2009).
9. Carabalona, A. et al. A glial origin for periventricular nodular heterotopia caused by impaired expression of flamin-A. Hum. Mol. Genet. 21, 1004-1017 (2012).
10. Lian, G. et al. Filamin A regulates neural progenitor proliferation and cortical size through Wee1-dependent Cdk1 phosphorylation. J. Neurosci. 32, 7672-7684 (2012).
11. Sheen, V.L. et al. Mutations in ARFGEF2 implicate vesicle traffcking in neural progenitor proliferation and migration in the human cerebral cortex. Nat. Genet. 36, 69-76 (2004).
12. Conti, V. et al. Periventricular heterotopia in 6q terminal deletion syndrome: role of the C6orf70 gene. Brain 136, 3378-3394 (2013).
13. Poirier, K. et al. Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly. Nat. Genet. 45, 639-647 (2013).
14. Mirzaa, G.M. et al. Characterisation of mutations of the phosphoinositide-3-kinase regulatory subunit, PIK3R2, in perisylvian polymicrogyria: a next-generation sequencing study. Lancet Neurol. 14, 1182-1195 (2015).
15. Kumar, S., Tomooka, Y. & Noda, M. Identifcation of a set of genes with developmentally down-regulated expression in the mouse brain. Biochem. Biophys. Res. Commun. 185, 1155-1161 (1992).
16. Sudol, M., Chen, H.I., Bougeret, C., Einbond, A. & Bork, P. Characterization of a novel protein-binding module-the WW domain. FEBS Lett. 369, 67-71 (1995).
17. 2+-binding domain. J. Biol. Chem. 273, 15879-15882 (1998).
18. Huang, L. et al. Structure of an E6AP-UbcH7 complex: insights into ubiquitination by the E2-E3 enzyme cascade. Science 286, 1321-1326 (1999).
19. Goel, P., Manning, J.A. & Kumar, S. NEDD4-2 (NEDD4L): the ubiquitin ligase for multiple membrane proteins. Gene 557, 1-10 (2015).
20. Garrone, N.F., Blazer-Yost, B.L., Weiss, R.B., Lalouel, J.M. & Rohrwasser, A. A human polymorphism affects NEDD4L subcellular targeting by leading to two isoforms that contain or lack a C2 domain. BMC Cell Biol. 10, 26 (2009).
21. Hsia, H.E. et al. Ubiquitin E3 ligase Nedd4-1 acts as a downstream target of PI3K/PTEN-mTORC1 signaling to promote neurite growth. Proc. Natl. Acad. Sci. USA 111, 13205-13210 (2014).
22. Franco, S.J., Martinez-Garay, I., Gil-Sanz, C., Harkins-Perry, S.R. & Müller, U. Reelin regulates cadherin function via Dab1/Rap1 to control neuronal migration and lamination in the neocortex. Neuron 69, 482-497 (2011).
23. Olson, E.C., Kim, S. & Walsh, C.A. Impaired neuronal positioning and dendritogenesis in the neocortex after cell-autonomous Dab1 suppression. J. Neurosci. 26, 1767-1775 (2006).
24. Sekine, K., Honda, T., Kawauchi, T., Kubo, K. & Nakajima, K. The outermost region of the developing cortical plate is crucial for both the switch of the radial migration mode and the Dab1-dependent "inside-out" lamination in the neocortex. J. Neurosci. 31, 9426-9439 (2011).
25. Sekine, K. et al. Reelin controls neuronal positioning by promoting cell-matrix adhesion via inside-out activation of integrin α5β1. Neuron 76, 353-369 (2012).
26. Lifton, R.P., Gharavi, A.G. & Geller, D.S. Molecular mechanisms of human hypertension. Cell 104, 545-556 (2001).
27. Boase, N.A. & Kumar, S. NEDD4: the founding member of a family of ubiquitin- protein ligases. Gene 557, 113-122 (2015).
28. Moon, U.Y. et al. Impaired reelin-Dab1 signaling contributes to neuronal migration defcits of tuberous sclerosis complex. Cell Rep. 12, 965-978 (2015).
29. Gao, S. et al. Ubiquitin ligase Nedd4L targets activated Smad2/3 to limit TGF-β signaling. Mol. Cell 36, 457-468 (2009).
30. Yu, J.S. et al. PI3K/mTORC2 regulates TGF-β/activin signalling by modulating Smad2/3 activity via linker phosphorylation. Nat. Commun. 6, 7212 (2015).
31. Wiesner, S. et al. Autoinhibition of the HECT-type ubiquitin ligase Smurf2 through its C2 domain. Cell 130, 651-662 (2007).
32. Bruce, M.C. et al. Regulation of Nedd4-2 self-ubiquitination and stability by a PY motif located within its HECT-domain. Biochem. J. 415, 155-163 (2008).
33. Wang, J. et al. Calcium activates Nedd4 E3 ubiquitin ligases by releasing the C2 domain-mediated auto-inhibition. J. Biol. Chem. 285, 12279-12288 (2010).
34. Escobedo, A. et al. Structural basis of the activation and degradation mechanisms of the E3 ubiquitin ligase Nedd4L. Structure 22, 1446-1457 (2014).
35. Honda, T. & Nakajima, K. Proper level of cytosolic disabled-1, which is regulated by dual nuclear translocation pathways, is important for cortical neuronal migration. Cereb. Cortex 26, 3219-3236 (2016).
36. Rivière, J.B. et al. De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. Nat. Genet. 44, 934-940 (2012).
37. Jansen, L.A. et al. PI3K/AKT pathway mutations cause a spectrum of brain malformations from megalencephaly to focal cortical dysplasia. Brain 138, 1613-1628 (2015).
38. Wright, C.F. et al. Genetic diagnosis of developmental disorders in the DDD study: a scalable analysis of genome-wide research data. Lancet 385, 1305-1314 (2015).
39. Cau, E., Gradwohl, G., Fode, C. & Guillemot, F. Mash1 activates a cascade of bHLH regulators in olfactory neuron progenitors. Development 124, 1611-1621 (1997).
40. Kielar, M. et al. Mutations in Eml1 lead to ectopic progenitors and neuronal heterotopia in mouse and human. Nat. Neurosci. 17, 923-933 (2014).