Kinesin-1, -2, and -3 motors use family-specific mechanochemical strategies to effectively compete with dynein during bidirectional transport
Bidirectional cargo transport in neurons requires competing activity of motors from the kinesin-1, -2, and -3 superfamilies against cytoplasmic dynein-1. Previous studies demonstrated that when kinesin-1 attached to dynein-dynactin-BicD2 (DDB) complex, the tethered motors move slowly with a slight p...
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| Format: | Article |
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eLife Sciences Publications Ltd
2022-09-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/82228 |
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| author | Allison M Gicking Tzu-Chen Ma Qingzhou Feng Rui Jiang Somayesadat Badieyan Michael A Cianfrocco William O Hancock |
| author_facet | Allison M Gicking Tzu-Chen Ma Qingzhou Feng Rui Jiang Somayesadat Badieyan Michael A Cianfrocco William O Hancock |
| author_sort | Allison M Gicking |
| collection | DOAJ |
| description | Bidirectional cargo transport in neurons requires competing activity of motors from the kinesin-1, -2, and -3 superfamilies against cytoplasmic dynein-1. Previous studies demonstrated that when kinesin-1 attached to dynein-dynactin-BicD2 (DDB) complex, the tethered motors move slowly with a slight plus-end bias, suggesting kinesin-1 overpowers DDB but DDB generates a substantial hindering load. Compared to kinesin-1, motors from the kinesin-2 and -3 families display a higher sensitivity to load in single-molecule assays and are thus predicted to be overpowered by dynein complexes in cargo transport. To test this prediction, we used a DNA scaffold to pair DDB with members of the kinesin-1, -2, and -3 families to recreate bidirectional transport in vitro, and tracked the motor pairs using two-channel TIRF microscopy. Unexpectedly, we find that when both kinesin and dynein are engaged and stepping on the microtubule, kinesin-1, -2, and -3 motors are able to effectively withstand hindering loads generated by DDB. Stochastic stepping simulations reveal that kinesin-2 and -3 motors compensate for their faster detachment rates under load with faster reattachment kinetics. The similar performance between the three kinesin transport families highlights how motor kinetics play critical roles in balancing forces between kinesin and dynein, and emphasizes the importance of motor regulation by cargo adaptors, regulatory proteins, and the microtubule track for tuning the speed and directionality of cargo transport in cells. |
| first_indexed | 2024-04-13T19:53:07Z |
| format | Article |
| id | doaj.art-c86cc14a186d4d8dad5f1b20dd34b118 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-13T19:53:07Z |
| publishDate | 2022-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c86cc14a186d4d8dad5f1b20dd34b1182022-12-22T02:32:27ZengeLife Sciences Publications LtdeLife2050-084X2022-09-011110.7554/eLife.82228Kinesin-1, -2, and -3 motors use family-specific mechanochemical strategies to effectively compete with dynein during bidirectional transportAllison M Gicking0https://orcid.org/0000-0002-9287-2580Tzu-Chen Ma1https://orcid.org/0000-0001-9896-8439Qingzhou Feng2Rui Jiang3https://orcid.org/0000-0001-6000-8512Somayesadat Badieyan4Michael A Cianfrocco5https://orcid.org/0000-0002-2067-4999William O Hancock6https://orcid.org/0000-0001-5547-8755Department of Biomedical Engineering, Pennsylvania State University, University Park, United StatesDepartment of Biomedical Engineering, Pennsylvania State University, University Park, United StatesDepartment of Biomedical Engineering, Pennsylvania State University, University Park, United StatesDepartment of Biomedical Engineering, Pennsylvania State University, University Park, United StatesDepartment of Biological Chemistry and the Life Sciences Institute, University of Michigan-Ann Arbor, Ann Arbor, United StatesDepartment of Biological Chemistry and the Life Sciences Institute, University of Michigan-Ann Arbor, Ann Arbor, United StatesDepartment of Biomedical Engineering, Pennsylvania State University, University Park, United StatesBidirectional cargo transport in neurons requires competing activity of motors from the kinesin-1, -2, and -3 superfamilies against cytoplasmic dynein-1. Previous studies demonstrated that when kinesin-1 attached to dynein-dynactin-BicD2 (DDB) complex, the tethered motors move slowly with a slight plus-end bias, suggesting kinesin-1 overpowers DDB but DDB generates a substantial hindering load. Compared to kinesin-1, motors from the kinesin-2 and -3 families display a higher sensitivity to load in single-molecule assays and are thus predicted to be overpowered by dynein complexes in cargo transport. To test this prediction, we used a DNA scaffold to pair DDB with members of the kinesin-1, -2, and -3 families to recreate bidirectional transport in vitro, and tracked the motor pairs using two-channel TIRF microscopy. Unexpectedly, we find that when both kinesin and dynein are engaged and stepping on the microtubule, kinesin-1, -2, and -3 motors are able to effectively withstand hindering loads generated by DDB. Stochastic stepping simulations reveal that kinesin-2 and -3 motors compensate for their faster detachment rates under load with faster reattachment kinetics. The similar performance between the three kinesin transport families highlights how motor kinetics play critical roles in balancing forces between kinesin and dynein, and emphasizes the importance of motor regulation by cargo adaptors, regulatory proteins, and the microtubule track for tuning the speed and directionality of cargo transport in cells.https://elifesciences.org/articles/82228bidirectional transportkinesindyneinmicrotubulecomputational modelingsingle-molecule |
| spellingShingle | Allison M Gicking Tzu-Chen Ma Qingzhou Feng Rui Jiang Somayesadat Badieyan Michael A Cianfrocco William O Hancock Kinesin-1, -2, and -3 motors use family-specific mechanochemical strategies to effectively compete with dynein during bidirectional transport eLife bidirectional transport kinesin dynein microtubule computational modeling single-molecule |
| title | Kinesin-1, -2, and -3 motors use family-specific mechanochemical strategies to effectively compete with dynein during bidirectional transport |
| title_full | Kinesin-1, -2, and -3 motors use family-specific mechanochemical strategies to effectively compete with dynein during bidirectional transport |
| title_fullStr | Kinesin-1, -2, and -3 motors use family-specific mechanochemical strategies to effectively compete with dynein during bidirectional transport |
| title_full_unstemmed | Kinesin-1, -2, and -3 motors use family-specific mechanochemical strategies to effectively compete with dynein during bidirectional transport |
| title_short | Kinesin-1, -2, and -3 motors use family-specific mechanochemical strategies to effectively compete with dynein during bidirectional transport |
| title_sort | kinesin 1 2 and 3 motors use family specific mechanochemical strategies to effectively compete with dynein during bidirectional transport |
| topic | bidirectional transport kinesin dynein microtubule computational modeling single-molecule |
| url | https://elifesciences.org/articles/82228 |
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