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Microtubule-associated septin complexes modulate kinesin and dynein motility with differential specificities

Long-range membrane traffic is guided by microtubule-associated proteins and posttranslational modifications, which collectively comprise a traffic code. The regulatory principles of this code and how it orchestrates the motility of kinesin and dynein motors are largely unknown. Septins are a large...

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Autores principales: Suber, Yani, Alam, Md Noor A., Nakos, Konstantinos, Bhakt, Priyanka, Spiliotis, Elias T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2023
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10463263/
https://www.ncbi.nlm.nih.gov/pubmed/37495111
http://dx.doi.org/10.1016/j.jbc.2023.105084
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author Suber, Yani
Alam, Md Noor A.
Nakos, Konstantinos
Bhakt, Priyanka
Spiliotis, Elias T.
author_facet Suber, Yani
Alam, Md Noor A.
Nakos, Konstantinos
Bhakt, Priyanka
Spiliotis, Elias T.
author_sort Suber, Yani
collection PubMed
description Long-range membrane traffic is guided by microtubule-associated proteins and posttranslational modifications, which collectively comprise a traffic code. The regulatory principles of this code and how it orchestrates the motility of kinesin and dynein motors are largely unknown. Septins are a large family of GTP-binding proteins, which assemble into complexes that associate with microtubules. Using single-molecule in vitro motility assays, we tested how the microtubule-associated SEPT2/6/7, SEPT2/6/7/9, and SEPT5/7/11 complexes affect the motilities of the constitutively active kinesins KIF5C and KIF1A and the dynein-dynactin-bicaudal D (DDB) motor complex. We found that microtubule-associated SEPT2/6/7 is a potent inhibitor of DDB and KIF5C, preventing mainly their association with microtubules. SEPT2/6/7 also inhibits KIF1A by obstructing stepping along microtubules. On SEPT2/6/7/9-coated microtubules, KIF1A inhibition is dampened by SEPT9, which alone enhances KIF1A, showing that individual septin subunits determine the regulatory properties of septin complexes. Strikingly, SEPT5/7/11 differs from SEPT2/6/7, in permitting the motility of KIF1A and immobilizing DDB to the microtubule lattice. In hippocampal neurons, filamentous SEPT5 colocalizes with somatodendritic microtubules that underlie Golgi membranes and lack SEPT6. Depletion of SEPT5 disrupts Golgi morphology and polarization of Golgi ribbons into the shaft of somato-proximal dendrites, which is consistent with the tethering of DDB to microtubules by SEPT5/7/11. Collectively, these results suggest that microtubule-associated complexes have differential specificities in the regulation of the motility and positioning of microtubule motors. We posit that septins are an integral part of the microtubule-based code that spatially controls membrane traffic.
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spelling pubmed-104632632023-08-30 Microtubule-associated septin complexes modulate kinesin and dynein motility with differential specificities Suber, Yani Alam, Md Noor A. Nakos, Konstantinos Bhakt, Priyanka Spiliotis, Elias T. J Biol Chem Research Article Long-range membrane traffic is guided by microtubule-associated proteins and posttranslational modifications, which collectively comprise a traffic code. The regulatory principles of this code and how it orchestrates the motility of kinesin and dynein motors are largely unknown. Septins are a large family of GTP-binding proteins, which assemble into complexes that associate with microtubules. Using single-molecule in vitro motility assays, we tested how the microtubule-associated SEPT2/6/7, SEPT2/6/7/9, and SEPT5/7/11 complexes affect the motilities of the constitutively active kinesins KIF5C and KIF1A and the dynein-dynactin-bicaudal D (DDB) motor complex. We found that microtubule-associated SEPT2/6/7 is a potent inhibitor of DDB and KIF5C, preventing mainly their association with microtubules. SEPT2/6/7 also inhibits KIF1A by obstructing stepping along microtubules. On SEPT2/6/7/9-coated microtubules, KIF1A inhibition is dampened by SEPT9, which alone enhances KIF1A, showing that individual septin subunits determine the regulatory properties of septin complexes. Strikingly, SEPT5/7/11 differs from SEPT2/6/7, in permitting the motility of KIF1A and immobilizing DDB to the microtubule lattice. In hippocampal neurons, filamentous SEPT5 colocalizes with somatodendritic microtubules that underlie Golgi membranes and lack SEPT6. Depletion of SEPT5 disrupts Golgi morphology and polarization of Golgi ribbons into the shaft of somato-proximal dendrites, which is consistent with the tethering of DDB to microtubules by SEPT5/7/11. Collectively, these results suggest that microtubule-associated complexes have differential specificities in the regulation of the motility and positioning of microtubule motors. We posit that septins are an integral part of the microtubule-based code that spatially controls membrane traffic. American Society for Biochemistry and Molecular Biology 2023-07-24 /pmc/articles/PMC10463263/ /pubmed/37495111 http://dx.doi.org/10.1016/j.jbc.2023.105084 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Suber, Yani
Alam, Md Noor A.
Nakos, Konstantinos
Bhakt, Priyanka
Spiliotis, Elias T.
Microtubule-associated septin complexes modulate kinesin and dynein motility with differential specificities
title Microtubule-associated septin complexes modulate kinesin and dynein motility with differential specificities
title_full Microtubule-associated septin complexes modulate kinesin and dynein motility with differential specificities
title_fullStr Microtubule-associated septin complexes modulate kinesin and dynein motility with differential specificities
title_full_unstemmed Microtubule-associated septin complexes modulate kinesin and dynein motility with differential specificities
title_short Microtubule-associated septin complexes modulate kinesin and dynein motility with differential specificities
title_sort microtubule-associated septin complexes modulate kinesin and dynein motility with differential specificities
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10463263/
https://www.ncbi.nlm.nih.gov/pubmed/37495111
http://dx.doi.org/10.1016/j.jbc.2023.105084
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