Fast axonal transport of the proteasome complex depends on membrane interaction and molecular motor function

Protein degradation by the ubiquitin-proteasome system in neurons depends on the correct delivery of the proteasome complex. In neurodegenerative diseases, aggregation and accumulation of proteins in axons link transport defects with degradation impairments; however, the transport properties of prot...

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Autores principales:	Otero, M.G., Alloatti, M., Cromberg, L.E., Almenar-Queralt, A., Encalada, S.E., Devoto, V.M.P., Bruno, L., Goldstein, L.S.B., Falzone, T.L.
Formato:	JOUR
Materias:	Axonal transport Kinesin-1 Membrane interaction Molecular motors Proteasome Vesicles molecular motor proteasome ubiquitin animal tissue article axoneme clearance controlled study degenerative disease diffusion Golgi complex in vivo study intracellular membrane lysosome mitochondrion molecular interaction motor unit mouse nerve fiber transport nonhuman priority journal protein degradation synapse vesicle viscoelasticity animal C57BL mouse cell culture cytology hippocampus metabolism nerve fiber physiology sciatic nerve synaptosome transport at the cellular level Animals Axonal Transport Axons Biological Transport Cells, Cultured Hippocampus Intracellular Membranes Mice Mice, Inbred C57BL Proteasome Endopeptidase Complex Sciatic Nerve Synaptic Vesicles Synaptosomes
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00219533_v127_n7_p1537_Otero
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_00219533_v127_n7_p1537_Otero
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spelling	todo:paper_00219533_v127_n7_p1537_Otero2023-10-03T14:23:34Z Fast axonal transport of the proteasome complex depends on membrane interaction and molecular motor function Otero, M.G. Alloatti, M. Cromberg, L.E. Almenar-Queralt, A. Encalada, S.E. Devoto, V.M.P. Bruno, L. Goldstein, L.S.B. Falzone, T.L. Axonal transport Kinesin-1 Membrane interaction Molecular motors Proteasome Vesicles molecular motor proteasome ubiquitin proteasome animal tissue article axoneme clearance controlled study degenerative disease diffusion Golgi complex in vivo study intracellular membrane lysosome mitochondrion molecular interaction motor unit mouse nerve fiber transport nonhuman priority journal protein degradation synapse vesicle viscoelasticity animal C57BL mouse cell culture cytology hippocampus intracellular membrane metabolism nerve fiber nerve fiber transport physiology sciatic nerve synaptosome transport at the cellular level Animals Axonal Transport Axons Biological Transport Cells, Cultured Hippocampus Intracellular Membranes Mice Mice, Inbred C57BL Proteasome Endopeptidase Complex Sciatic Nerve Synaptic Vesicles Synaptosomes Protein degradation by the ubiquitin-proteasome system in neurons depends on the correct delivery of the proteasome complex. In neurodegenerative diseases, aggregation and accumulation of proteins in axons link transport defects with degradation impairments; however, the transport properties of proteasomes remain unknown. Here, using in vivo experiments, we reveal the fast anterograde transport of assembled and functional 26S proteasome complexes. A high-resolution tracking system to follow fluorescent proteasomes revealed three types of motion: actively driven proteasome axonal transport, diffusive behavior in a viscoelastic axonema and proteasome-confined motion. We show that active proteasome transport depends on motor function because knockdown of the KIF5B motor subunit resulted in impairment of the anterograde proteasome flux and the density of segmental velocities. Finally, we reveal that neuronal proteasomes interact with intracellular membranes and identify the coordinated transport of fluorescent proteasomes with synaptic precursor vesicles, Golgi-derived vesicles, lysosomes and mitochondria. Taken together, our results reveal fast axonal transport as a new mechanism of proteasome delivery that depends on membrane cargo 'hitch-hiking' and the function of molecular motors. We further hypothesize that defects in proteasome transport could promote abnormal protein clearance in neurodegenerative diseases. © 2014.Published by The Company of Biologists Ltd. Fil:Cromberg, L.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Bruno, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Falzone, T.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00219533_v127_n7_p1537_Otero
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Axonal transport Kinesin-1 Membrane interaction Molecular motors Proteasome Vesicles molecular motor proteasome ubiquitin proteasome animal tissue article axoneme clearance controlled study degenerative disease diffusion Golgi complex in vivo study intracellular membrane lysosome mitochondrion molecular interaction motor unit mouse nerve fiber transport nonhuman priority journal protein degradation synapse vesicle viscoelasticity animal C57BL mouse cell culture cytology hippocampus intracellular membrane metabolism nerve fiber nerve fiber transport physiology sciatic nerve synaptosome transport at the cellular level Animals Axonal Transport Axons Biological Transport Cells, Cultured Hippocampus Intracellular Membranes Mice Mice, Inbred C57BL Proteasome Endopeptidase Complex Sciatic Nerve Synaptic Vesicles Synaptosomes
spellingShingle	Axonal transport Kinesin-1 Membrane interaction Molecular motors Proteasome Vesicles molecular motor proteasome ubiquitin proteasome animal tissue article axoneme clearance controlled study degenerative disease diffusion Golgi complex in vivo study intracellular membrane lysosome mitochondrion molecular interaction motor unit mouse nerve fiber transport nonhuman priority journal protein degradation synapse vesicle viscoelasticity animal C57BL mouse cell culture cytology hippocampus intracellular membrane metabolism nerve fiber nerve fiber transport physiology sciatic nerve synaptosome transport at the cellular level Animals Axonal Transport Axons Biological Transport Cells, Cultured Hippocampus Intracellular Membranes Mice Mice, Inbred C57BL Proteasome Endopeptidase Complex Sciatic Nerve Synaptic Vesicles Synaptosomes Otero, M.G. Alloatti, M. Cromberg, L.E. Almenar-Queralt, A. Encalada, S.E. Devoto, V.M.P. Bruno, L. Goldstein, L.S.B. Falzone, T.L. Fast axonal transport of the proteasome complex depends on membrane interaction and molecular motor function
topic_facet	Axonal transport Kinesin-1 Membrane interaction Molecular motors Proteasome Vesicles molecular motor proteasome ubiquitin proteasome animal tissue article axoneme clearance controlled study degenerative disease diffusion Golgi complex in vivo study intracellular membrane lysosome mitochondrion molecular interaction motor unit mouse nerve fiber transport nonhuman priority journal protein degradation synapse vesicle viscoelasticity animal C57BL mouse cell culture cytology hippocampus intracellular membrane metabolism nerve fiber nerve fiber transport physiology sciatic nerve synaptosome transport at the cellular level Animals Axonal Transport Axons Biological Transport Cells, Cultured Hippocampus Intracellular Membranes Mice Mice, Inbred C57BL Proteasome Endopeptidase Complex Sciatic Nerve Synaptic Vesicles Synaptosomes
description	Protein degradation by the ubiquitin-proteasome system in neurons depends on the correct delivery of the proteasome complex. In neurodegenerative diseases, aggregation and accumulation of proteins in axons link transport defects with degradation impairments; however, the transport properties of proteasomes remain unknown. Here, using in vivo experiments, we reveal the fast anterograde transport of assembled and functional 26S proteasome complexes. A high-resolution tracking system to follow fluorescent proteasomes revealed three types of motion: actively driven proteasome axonal transport, diffusive behavior in a viscoelastic axonema and proteasome-confined motion. We show that active proteasome transport depends on motor function because knockdown of the KIF5B motor subunit resulted in impairment of the anterograde proteasome flux and the density of segmental velocities. Finally, we reveal that neuronal proteasomes interact with intracellular membranes and identify the coordinated transport of fluorescent proteasomes with synaptic precursor vesicles, Golgi-derived vesicles, lysosomes and mitochondria. Taken together, our results reveal fast axonal transport as a new mechanism of proteasome delivery that depends on membrane cargo 'hitch-hiking' and the function of molecular motors. We further hypothesize that defects in proteasome transport could promote abnormal protein clearance in neurodegenerative diseases. © 2014.Published by The Company of Biologists Ltd.
format	JOUR
author	Otero, M.G. Alloatti, M. Cromberg, L.E. Almenar-Queralt, A. Encalada, S.E. Devoto, V.M.P. Bruno, L. Goldstein, L.S.B. Falzone, T.L.
author_facet	Otero, M.G. Alloatti, M. Cromberg, L.E. Almenar-Queralt, A. Encalada, S.E. Devoto, V.M.P. Bruno, L. Goldstein, L.S.B. Falzone, T.L.
author_sort	Otero, M.G.
title	Fast axonal transport of the proteasome complex depends on membrane interaction and molecular motor function
title_short	Fast axonal transport of the proteasome complex depends on membrane interaction and molecular motor function
title_full	Fast axonal transport of the proteasome complex depends on membrane interaction and molecular motor function
title_fullStr	Fast axonal transport of the proteasome complex depends on membrane interaction and molecular motor function
title_full_unstemmed	Fast axonal transport of the proteasome complex depends on membrane interaction and molecular motor function
title_sort	fast axonal transport of the proteasome complex depends on membrane interaction and molecular motor function
url	http://hdl.handle.net/20.500.12110/paper_00219533_v127_n7_p1537_Otero
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_version_	1782027657974644736

Fast axonal transport of the proteasome complex depends on membrane interaction and molecular motor function

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