@article{eb03635f2c0e4d2f8ecc3d8fc4f4c0c4,
title = "A novel ALS-associated variant in UBQLN4 regulates motor axon morphogenesis",
abstract = "The etiological underpinnings of amyotrophic lateral sclerosis (ALS) are complex and incompletely understood, although contributions to pathogenesis by regulators of proteolytic pathways have become increasingly apparent. Here, we present a novel variant in UBQLN4 that is associated with ALS and show that its expression compromises motor axon morphogenesis in mouse motor neurons and in zebrafish. We further demonstrate that the ALS-associated UBQLN4 variant impairs proteasomal function, and identify the Wnt signaling pathway effector beta-catenin as a UBQLN4 substrate. Inhibition of beta-catenin function rescues the UBQLN4 variant-induced motor axon phenotypes. These findings provide a strong link between the regulation of axonal morphogenesis and a new ALS-associated gene variant mediated by protein degradation pathways.",
author = "Edens, {Brittany M.} and Jianhua Yan and Nimrod Miller and Deng, {Han Xiang} and Teepu Siddique and Ma, {Yongchao C.}",
note = "Funding Information: This work was supported by NIH grants NS094564, AG043970 and grants from The Hartwell Foundation and Whitehall Foundation (YCM); NS078504, NS078504, Les Turner ALS Foundation, the Foglia Family Fund for ALS Research, Les Turner ALS Foundation/Herbert C Wenske Foundation Professorship, Vena E Schaff ALS Research Fund, and SP Foundation (TS). YCM is Ann Marie and Francis Klocke MD Research Scholar supported by the Joseph and Bessie Feinberg Foundation. National Institute of Neuroloical Disorders and Stroke NS094564 Yongchao C Ma National Institute on Aging AG043970 Yongchao C Ma The Hartwell Foundation Yongchao C Ma Whitehall Foundation Yongchao C Ma National Institute of Neurological Disorders and Stroke NS078504 Teepu Siddique Les Turner ALS Foundation Teepu Siddique. Publisher Copyright: {\textcopyright} Edens et al. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.",
year = "2017",
month = may,
day = "2",
doi = "10.7554/eLife.25453",
language = "English (US)",
volume = "6",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}