The Experts below are selected from a list of 1218 Experts worldwide ranked by ideXlab platform
Jordan E Burke - One of the best experts on this subject based on the ideXlab platform.
-
pathogenic tfg mutations underlying hereditary spastic paraplegia impair secretory protein trafficking and Axon Fasciculation
Cell Reports, 2018Co-Authors: Erin L Slosarek, Amber L Schuh, Iryna Pustova, Adam Johnson, Jennifer Bird, Matthew C Johnson, E B Frankel, Nilakshee Bhattacharya, Michael Hanna, Jordan E BurkeAbstract:Length-dependent Axonopathy of the corticospinal tract causes lower limb spasticity and is characteristic of several neurological disorders, including hereditary spastic paraplegia (HSP) and amyotrophic lateral sclerosis. Mutations in Trk-fused gene (TFG) have been implicated in both diseases, but the pathomechanisms by which these alterations cause neuropathy remain unclear. Here, we biochemically and genetically define the impact of a mutation within the TFG coiled-coil domain, which underlies early-onset forms of HSP. We find that the TFG (p.R106C) mutation alters compaction of TFG ring complexes, which play a critical role in the export of cargoes from the endoplasmic reticulum (ER). Using CRISPR-mediated genome editing, we engineered human stem cells that express the mutant form of TFG at endogenous levels and identified specific defects in secretion from the ER and Axon Fasciculation following neuronal differentiation. Together, our data highlight a key role for TFG-mediated protein transport in the pathogenesis of HSP.
-
pathogenic tfg mutations underlying hereditary spastic paraplegia impair secretory protein trafficking and Axon Fasciculation
Social Science Research Network, 2018Co-Authors: Erin L Slosarek, Amber L Schuh, Adam Johnson, Jennifer Bird, Matthew C Johnson, Nilakshee Bhattacharya, Jordan E Burke, E B Franke, Michael G Hanna, David A RuhlAbstract:Length-dependent Axonopathy of the corticospinal tract causes lower limb spasticity and weakness and is characteristic of several neurological disorders, including hereditary spastic paraplegia (HSP) and amyotrophic lateral sclerosis (ALS). Mutations in tropomyosin-receptor kinase fused gene (TFG) have been implicated in both disease states, but the pathomechanisms by which these alterations cause neuropathy remain unclear. Here, we biochemically and genetically define the impact of a mutation within the coiled coil domain of TFG, which underlies early onset forms of HSP. We find that the TFG (p.R106C) mutation alters compaction of TFG ring complexes, which play a critical role in the export of cargoes from the endoplasmic reticulum (ER). Moreover, using CRISPR-mediated genome editing, we engineered human stem cells that express the mutant form of TFG at endogenous levels and identified specific defects in secretion from the ER and Axon Fasciculation following neuronal differentiation. Together, our data highlight a key role for TFG-mediated protein transport in the pathogenesis of HSP.
Erin L Slosarek - One of the best experts on this subject based on the ideXlab platform.
-
pathogenic tfg mutations underlying hereditary spastic paraplegia impair secretory protein trafficking and Axon Fasciculation
Cell Reports, 2018Co-Authors: Erin L Slosarek, Amber L Schuh, Iryna Pustova, Adam Johnson, Jennifer Bird, Matthew C Johnson, E B Frankel, Nilakshee Bhattacharya, Michael Hanna, Jordan E BurkeAbstract:Length-dependent Axonopathy of the corticospinal tract causes lower limb spasticity and is characteristic of several neurological disorders, including hereditary spastic paraplegia (HSP) and amyotrophic lateral sclerosis. Mutations in Trk-fused gene (TFG) have been implicated in both diseases, but the pathomechanisms by which these alterations cause neuropathy remain unclear. Here, we biochemically and genetically define the impact of a mutation within the TFG coiled-coil domain, which underlies early-onset forms of HSP. We find that the TFG (p.R106C) mutation alters compaction of TFG ring complexes, which play a critical role in the export of cargoes from the endoplasmic reticulum (ER). Using CRISPR-mediated genome editing, we engineered human stem cells that express the mutant form of TFG at endogenous levels and identified specific defects in secretion from the ER and Axon Fasciculation following neuronal differentiation. Together, our data highlight a key role for TFG-mediated protein transport in the pathogenesis of HSP.
-
pathogenic tfg mutations underlying hereditary spastic paraplegia impair secretory protein trafficking and Axon Fasciculation
Social Science Research Network, 2018Co-Authors: Erin L Slosarek, Amber L Schuh, Adam Johnson, Jennifer Bird, Matthew C Johnson, Nilakshee Bhattacharya, Jordan E Burke, E B Franke, Michael G Hanna, David A RuhlAbstract:Length-dependent Axonopathy of the corticospinal tract causes lower limb spasticity and weakness and is characteristic of several neurological disorders, including hereditary spastic paraplegia (HSP) and amyotrophic lateral sclerosis (ALS). Mutations in tropomyosin-receptor kinase fused gene (TFG) have been implicated in both disease states, but the pathomechanisms by which these alterations cause neuropathy remain unclear. Here, we biochemically and genetically define the impact of a mutation within the coiled coil domain of TFG, which underlies early onset forms of HSP. We find that the TFG (p.R106C) mutation alters compaction of TFG ring complexes, which play a critical role in the export of cargoes from the endoplasmic reticulum (ER). Moreover, using CRISPR-mediated genome editing, we engineered human stem cells that express the mutant form of TFG at endogenous levels and identified specific defects in secretion from the ER and Axon Fasciculation following neuronal differentiation. Together, our data highlight a key role for TFG-mediated protein transport in the pathogenesis of HSP.
David A Ruhl - One of the best experts on this subject based on the ideXlab platform.
-
pathogenic tfg mutations underlying hereditary spastic paraplegia impair secretory protein trafficking and Axon Fasciculation
Social Science Research Network, 2018Co-Authors: Erin L Slosarek, Amber L Schuh, Adam Johnson, Jennifer Bird, Matthew C Johnson, Nilakshee Bhattacharya, Jordan E Burke, E B Franke, Michael G Hanna, David A RuhlAbstract:Length-dependent Axonopathy of the corticospinal tract causes lower limb spasticity and weakness and is characteristic of several neurological disorders, including hereditary spastic paraplegia (HSP) and amyotrophic lateral sclerosis (ALS). Mutations in tropomyosin-receptor kinase fused gene (TFG) have been implicated in both disease states, but the pathomechanisms by which these alterations cause neuropathy remain unclear. Here, we biochemically and genetically define the impact of a mutation within the coiled coil domain of TFG, which underlies early onset forms of HSP. We find that the TFG (p.R106C) mutation alters compaction of TFG ring complexes, which play a critical role in the export of cargoes from the endoplasmic reticulum (ER). Moreover, using CRISPR-mediated genome editing, we engineered human stem cells that express the mutant form of TFG at endogenous levels and identified specific defects in secretion from the ER and Axon Fasciculation following neuronal differentiation. Together, our data highlight a key role for TFG-mediated protein transport in the pathogenesis of HSP.
Nilakshee Bhattacharya - One of the best experts on this subject based on the ideXlab platform.
-
pathogenic tfg mutations underlying hereditary spastic paraplegia impair secretory protein trafficking and Axon Fasciculation
Cell Reports, 2018Co-Authors: Erin L Slosarek, Amber L Schuh, Iryna Pustova, Adam Johnson, Jennifer Bird, Matthew C Johnson, E B Frankel, Nilakshee Bhattacharya, Michael Hanna, Jordan E BurkeAbstract:Length-dependent Axonopathy of the corticospinal tract causes lower limb spasticity and is characteristic of several neurological disorders, including hereditary spastic paraplegia (HSP) and amyotrophic lateral sclerosis. Mutations in Trk-fused gene (TFG) have been implicated in both diseases, but the pathomechanisms by which these alterations cause neuropathy remain unclear. Here, we biochemically and genetically define the impact of a mutation within the TFG coiled-coil domain, which underlies early-onset forms of HSP. We find that the TFG (p.R106C) mutation alters compaction of TFG ring complexes, which play a critical role in the export of cargoes from the endoplasmic reticulum (ER). Using CRISPR-mediated genome editing, we engineered human stem cells that express the mutant form of TFG at endogenous levels and identified specific defects in secretion from the ER and Axon Fasciculation following neuronal differentiation. Together, our data highlight a key role for TFG-mediated protein transport in the pathogenesis of HSP.
-
pathogenic tfg mutations underlying hereditary spastic paraplegia impair secretory protein trafficking and Axon Fasciculation
Social Science Research Network, 2018Co-Authors: Erin L Slosarek, Amber L Schuh, Adam Johnson, Jennifer Bird, Matthew C Johnson, Nilakshee Bhattacharya, Jordan E Burke, E B Franke, Michael G Hanna, David A RuhlAbstract:Length-dependent Axonopathy of the corticospinal tract causes lower limb spasticity and weakness and is characteristic of several neurological disorders, including hereditary spastic paraplegia (HSP) and amyotrophic lateral sclerosis (ALS). Mutations in tropomyosin-receptor kinase fused gene (TFG) have been implicated in both disease states, but the pathomechanisms by which these alterations cause neuropathy remain unclear. Here, we biochemically and genetically define the impact of a mutation within the coiled coil domain of TFG, which underlies early onset forms of HSP. We find that the TFG (p.R106C) mutation alters compaction of TFG ring complexes, which play a critical role in the export of cargoes from the endoplasmic reticulum (ER). Moreover, using CRISPR-mediated genome editing, we engineered human stem cells that express the mutant form of TFG at endogenous levels and identified specific defects in secretion from the ER and Axon Fasciculation following neuronal differentiation. Together, our data highlight a key role for TFG-mediated protein transport in the pathogenesis of HSP.
Amber L Schuh - One of the best experts on this subject based on the ideXlab platform.
-
pathogenic tfg mutations underlying hereditary spastic paraplegia impair secretory protein trafficking and Axon Fasciculation
Cell Reports, 2018Co-Authors: Erin L Slosarek, Amber L Schuh, Iryna Pustova, Adam Johnson, Jennifer Bird, Matthew C Johnson, E B Frankel, Nilakshee Bhattacharya, Michael Hanna, Jordan E BurkeAbstract:Length-dependent Axonopathy of the corticospinal tract causes lower limb spasticity and is characteristic of several neurological disorders, including hereditary spastic paraplegia (HSP) and amyotrophic lateral sclerosis. Mutations in Trk-fused gene (TFG) have been implicated in both diseases, but the pathomechanisms by which these alterations cause neuropathy remain unclear. Here, we biochemically and genetically define the impact of a mutation within the TFG coiled-coil domain, which underlies early-onset forms of HSP. We find that the TFG (p.R106C) mutation alters compaction of TFG ring complexes, which play a critical role in the export of cargoes from the endoplasmic reticulum (ER). Using CRISPR-mediated genome editing, we engineered human stem cells that express the mutant form of TFG at endogenous levels and identified specific defects in secretion from the ER and Axon Fasciculation following neuronal differentiation. Together, our data highlight a key role for TFG-mediated protein transport in the pathogenesis of HSP.
-
pathogenic tfg mutations underlying hereditary spastic paraplegia impair secretory protein trafficking and Axon Fasciculation
Social Science Research Network, 2018Co-Authors: Erin L Slosarek, Amber L Schuh, Adam Johnson, Jennifer Bird, Matthew C Johnson, Nilakshee Bhattacharya, Jordan E Burke, E B Franke, Michael G Hanna, David A RuhlAbstract:Length-dependent Axonopathy of the corticospinal tract causes lower limb spasticity and weakness and is characteristic of several neurological disorders, including hereditary spastic paraplegia (HSP) and amyotrophic lateral sclerosis (ALS). Mutations in tropomyosin-receptor kinase fused gene (TFG) have been implicated in both disease states, but the pathomechanisms by which these alterations cause neuropathy remain unclear. Here, we biochemically and genetically define the impact of a mutation within the coiled coil domain of TFG, which underlies early onset forms of HSP. We find that the TFG (p.R106C) mutation alters compaction of TFG ring complexes, which play a critical role in the export of cargoes from the endoplasmic reticulum (ER). Moreover, using CRISPR-mediated genome editing, we engineered human stem cells that express the mutant form of TFG at endogenous levels and identified specific defects in secretion from the ER and Axon Fasciculation following neuronal differentiation. Together, our data highlight a key role for TFG-mediated protein transport in the pathogenesis of HSP.