Journal article

Seizures Are Regulated by Ubiquitin-specific Peptidase 9 X-linked (USP9X), a De-Ubiquitinase

Lily Paemka, Vinit B Mahajan, Salleh N Ehaideb, Jessica M Skeie, Men Chee Tan, Shu Wu, Allison J Cox, Levi P Sowers, Jozef Gecz, Lachlan Jolly, Polly J Ferguson, Benjamin Darbro, Amy Schneider, Ingrid E Scheffer, Gemma L Carvill, Heather C Mefford, Hatem El-Shanti, Stephen A Wood, J Robert Manak, Alexander G Bassuk

PLOS GENETICS | PUBLIC LIBRARY SCIENCE | Published : 2015

Abstract

Epilepsy is a common disabling disease with complex, multifactorial genetic and environmental etiology. The small fraction of epilepsies subject to Mendelian inheritance offers key insight into epilepsy disease mechanisms; and pathologies brought on by mutations in a single gene can point the way to generalizable therapeutic strategies. Mutations in the PRICKLE genes can cause seizures in humans, zebrafish, mice, and flies, suggesting the seizure-suppression pathway is evolutionarily conserved. This pathway has never been targeted for novel anti-seizure treatments. Here, the mammalian PRICKLE-interactome was defined, identifying prickle-interacting proteins that localize to synapses and a no..

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Grants

Awarded by National Institutes of Health


Awarded by Qatar National Research Fund


Awarded by NHMRC


Awarded by EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT


Awarded by NATIONAL EYE INSTITUTE


Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES


Awarded by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE


Funding Acknowledgements

This work was supported by 1. National Institutes of Health (http://www.nih.gov/) 1R01 NS064159-01A1 and 5R21MH100086-02 (to AGB). 2. Qatar National Research Fund (http://www.qnrf.org/en-us) 6-359-3-095 (to HES). 3. NHMRC Program Grant 628952 and NHMRC Senior Research Fellowship 1041920 to JG. 4. National Institutes of Health (http://www.nih.gov/) R56 NS068605-05 to HCM. 5. National Institutes of Health (http://www.nih.gov/) to PJF. 6. King Abdullah International Medical Research Center, King Abdulaziz Medical City, Riyadh, KSA to SNE. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.