Pathogenic TFG Mutations Underlying Hereditary Spastic Paraplegia Impair Secretory Protein Trafficking and Axon Fasciculation
作者： Erin L. Slosarek , Amber L. Schuh , Iryna Pustova , Adam Johnson , Jennifer Bird
DOI: 10.1016/J.CELREP.2018.07.081
关键词:
摘要: Length-dependent axonopathy of the corticospinal tract causes lower limb spasticity and is characteristic several neurological disorders, including hereditary spastic paraplegia (HSP) amyotrophic lateral sclerosis. Mutations in Trk-fused gene (TFG) have been implicated both diseases, but pathomechanisms by which these alterations cause neuropathy remain unclear. Here, we biochemically genetically define impact a mutation within TFG coiled-coil domain, underlies early-onset forms HSP. We find that (p.R106C) alters compaction ring complexes, which play critical role export cargoes from endoplasmic reticulum (ER). Using CRISPR-mediated genome editing, engineered human stem cells express mutant form at endogenous levels identified specific defects secretion ER axon fasciculation following neuronal differentiation. Together, our data highlight key for TFG-mediated protein transport pathogenesis
fsu.edu
elsevier.com参考文章(48)
Malene Winther, Peter S. Walmod, Neural cell adhesion molecules belonging to the family of leucine-rich repeat proteins. Advances in neurobiology. ,vol. 8, pp. 315- 395 ,(2014) , 10.1007/978-1-4614-8090-7_14
Wiep Scheper, Jeroen J. M. Hoozemans, The unfolded protein response in neurodegenerative diseases: a neuropathological perspective. Acta Neuropathologica. ,vol. 130, pp. 315- 331 ,(2015) , 10.1007/S00401-015-1462-8
John F. Presley, Nelson B. Cole, Trina A. Schroer, Koret Hirschberg, Kristien J. M. Zaal, Jennifer Lippincott-Schwartz, ER-to-Golgi transport visualized in living cells Nature. ,vol. 389, pp. 81- 85 ,(1997) , 10.1038/38001
Jia‐Rong Jheng, Kean Seng Lau, Wen‐Fang Tang, Ming‐sian Wu, Jim‐Tong Horng, None, Endoplasmic reticulum stress is induced and modulated by enterovirus 71. Cellular Microbiology. ,vol. 12, pp. 796- 813 ,(2010) , 10.1111/J.1462-5822.2010.01434.X
Kyle R. Denton, Ling Lei, Jeremy Grenier, Vladimir Rodionov, Craig Blackstone, Xue-Jun Li, Loss of spastin function results in disease-specific axonal defects in human pluripotent stem cell-based models of hereditary spastic paraplegia Stem Cells. ,vol. 32, pp. 414- 423 ,(2014) , 10.1002/STEM.1569
Hiroyuki Ishiura, Wataru Sako, Mari Yoshida, Toshitaka Kawarai, Osamu Tanabe, Jun Goto, Yuji Takahashi, Hidetoshi Date, Jun Mitsui, Budrul Ahsan, Yaeko Ichikawa, Atsushi Iwata, Hiide Yoshino, Yuishin Izumi, Koji Fujita, Kouji Maeda, Satoshi Goto, Hidetaka Koizumi, Ryoma Morigaki, Masako Ikemura, Naoko Yamauchi, Shigeo Murayama, Garth A. Nicholson, Hidefumi Ito, Gen Sobue, Masanori Nakagawa, Ryuji Kaji, Shoji Tsuji, The TRK-Fused Gene Is Mutated in Hereditary Motor and Sensory Neuropathy with Proximal Dominant Involvement American Journal of Human Genetics. ,vol. 91, pp. 320- 329 ,(2012) , 10.1016/J.AJHG.2012.07.014
Toshitaka Kawarai, Mitsuya Morita, Ryoma Morigaki, Koji Fujita, Hiroyuki Nodera, Yuishin Izumi, Satoshi Goto, Imaharu Nakano, Ryuji Kaji, Pathomechanisms of motor neuron death by mutant TFG Rinsho Shinkeigaku. ,vol. 53, pp. 1199- ,(2013) , 10.5692/CLINICALNEUROL.53.1199
J Wu, R J Kaufman, From acute ER stress to physiological roles of the Unfolded Protein Response. Cell Death & Differentiation. ,vol. 13, pp. 374- 384 ,(2006) , 10.1038/SJ.CDD.4401840
Filippo Prischi, Piotr R Nowak, Marta Carrara, Maruf MU Ali, None, Phosphoregulation of Ire1 RNase splicing activity Nature Communications. ,vol. 5, pp. 3554- 3554 ,(2014) , 10.1038/NCOMMS4554
Monique Jouet, André Rosenthal, Giles Armstrong, John MacFarlane, Roger Stevenson, Joan Paterson, Aïda Metzenberg, Victor Ionasescu, Karen Temple, Susan Kenwrick, X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene Nature Genetics. ,vol. 7, pp. 402- 407 ,(1994) , 10.1038/NG0794-402