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Microtubule-associated septin complexes modulate kinesin and dynein motility with differential specificities
Journal article   Open access   Peer reviewed

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

Yani Suber, Md Noor A. Alam, Konstantinos Nakos, Priyanka Bhakt and Elias T. Spiliotis
The Journal of biological chemistry, 105084
24 Jul 2023
DOI: https://doi.org/10.1016/j.jbc.2023.105084
url
https://doi.org/10.1016/j.jbc.2023.105084View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

dynein Golgi kinesin membrane traffic microtubule-associated proteins microtubules neurons septins
Long-range membrane traffic is guided by microtubule-associated proteins (MAPs) and post-translational 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-BiCD2 (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 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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