MAP7 regulates axon morphogenesis by recruiting kinesin-1 to microtubules and modulating organelle transport
Neuronal cell morphogenesis depends on proper regulation of microtubule-based transport, but the underlying mechanisms are not well understood. Here, we report our study of MAP7, a unique microtubule-associated protein that interacts with both microtubules and the motor protein kinesin-1. Structure-...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-08-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/36374 |
| _version_ | 1797997592845484032 |
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| author | Stephen R Tymanskyj Benjamin H Yang Kristen J Verhey Le Ma |
| author_facet | Stephen R Tymanskyj Benjamin H Yang Kristen J Verhey Le Ma |
| author_sort | Stephen R Tymanskyj |
| collection | DOAJ |
| description | Neuronal cell morphogenesis depends on proper regulation of microtubule-based transport, but the underlying mechanisms are not well understood. Here, we report our study of MAP7, a unique microtubule-associated protein that interacts with both microtubules and the motor protein kinesin-1. Structure-function analysis in rat embryonic sensory neurons shows that the kinesin-1 interacting domain in MAP7 is required for axon and branch growth but not for branch formation. Also, two unique microtubule binding sites are found in MAP7 that have distinct dissociation kinetics and are both required for branch formation. Furthermore, MAP7 recruits kinesin-1 dynamically to microtubules, leading to alterations in organelle transport behaviors, particularly pause/speed switching. As MAP7 is localized to branch sites, our results suggest a novel mechanism mediated by the dual interactions of MAP7 with microtubules and kinesin-1 in the precise control of microtubule-based transport during axon morphogenesis. |
| first_indexed | 2024-04-11T10:35:14Z |
| format | Article |
| id | doaj.art-f65754813a954758951acd2823ca9cb0 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T10:35:14Z |
| publishDate | 2018-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-f65754813a954758951acd2823ca9cb02022-12-22T04:29:20ZengeLife Sciences Publications LtdeLife2050-084X2018-08-01710.7554/eLife.36374MAP7 regulates axon morphogenesis by recruiting kinesin-1 to microtubules and modulating organelle transportStephen R Tymanskyj0https://orcid.org/0000-0002-6837-0644Benjamin H Yang1https://orcid.org/0000-0002-9845-0514Kristen J Verhey2https://orcid.org/0000-0001-9329-4981Le Ma3https://orcid.org/0000-0003-2769-9416Jefferson Synaptic Biology Center, Vickie and Jack Farber Institute for Neuroscience, Thomas Jefferson University, Philadelphia, United States; Department of Neuroscience, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, United StatesJefferson Synaptic Biology Center, Vickie and Jack Farber Institute for Neuroscience, Thomas Jefferson University, Philadelphia, United States; Department of Neuroscience, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, United StatesDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United StatesJefferson Synaptic Biology Center, Vickie and Jack Farber Institute for Neuroscience, Thomas Jefferson University, Philadelphia, United States; Department of Neuroscience, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, United StatesNeuronal cell morphogenesis depends on proper regulation of microtubule-based transport, but the underlying mechanisms are not well understood. Here, we report our study of MAP7, a unique microtubule-associated protein that interacts with both microtubules and the motor protein kinesin-1. Structure-function analysis in rat embryonic sensory neurons shows that the kinesin-1 interacting domain in MAP7 is required for axon and branch growth but not for branch formation. Also, two unique microtubule binding sites are found in MAP7 that have distinct dissociation kinetics and are both required for branch formation. Furthermore, MAP7 recruits kinesin-1 dynamically to microtubules, leading to alterations in organelle transport behaviors, particularly pause/speed switching. As MAP7 is localized to branch sites, our results suggest a novel mechanism mediated by the dual interactions of MAP7 with microtubules and kinesin-1 in the precise control of microtubule-based transport during axon morphogenesis.https://elifesciences.org/articles/36374axon growth and branchingkinesin-1MAP7microtubulemitochondrial transport |
| spellingShingle | Stephen R Tymanskyj Benjamin H Yang Kristen J Verhey Le Ma MAP7 regulates axon morphogenesis by recruiting kinesin-1 to microtubules and modulating organelle transport eLife axon growth and branching kinesin-1 MAP7 microtubule mitochondrial transport |
| title | MAP7 regulates axon morphogenesis by recruiting kinesin-1 to microtubules and modulating organelle transport |
| title_full | MAP7 regulates axon morphogenesis by recruiting kinesin-1 to microtubules and modulating organelle transport |
| title_fullStr | MAP7 regulates axon morphogenesis by recruiting kinesin-1 to microtubules and modulating organelle transport |
| title_full_unstemmed | MAP7 regulates axon morphogenesis by recruiting kinesin-1 to microtubules and modulating organelle transport |
| title_short | MAP7 regulates axon morphogenesis by recruiting kinesin-1 to microtubules and modulating organelle transport |
| title_sort | map7 regulates axon morphogenesis by recruiting kinesin 1 to microtubules and modulating organelle transport |
| topic | axon growth and branching kinesin-1 MAP7 microtubule mitochondrial transport |
| url | https://elifesciences.org/articles/36374 |
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