Regulation of mitochondria-dynactin interaction and mitochondrial retrograde transport in axons
Abstract
Mitochondrial transport in axons is critical for neural circuit health and function. While several proteins have been found that modulate bidirectional mitochondrial motility, factors that regulate unidirectional mitochondrial transport have been harder to identify. In a genetic screen, we found a zebrafish strain in which mitochondria fail to attach to the dynein retrograde motor. This strain carries a loss-of-function mutation in actr10, a member of the dynein-associated complex dynactin. The abnormal axon morphology and mitochondrial retrograde transport defects observed in actr10 mutants are distinct from dynein and dynactin mutant axonal phenotypes. In addition, Actr10 lacking the dynactin binding domain maintains its ability to bind mitochondria, arguing for a role for Actr10 in dynactin-mitochondria interaction. Finally, genetic interaction studies implicated Drp1 as a partner in Actr10-dependent mitochondrial retrograde transport. Together, this work identifies Actr10 as a factor necessary for dynactin-mitochondria interaction, enhancing our understanding of how mitochondria properly localize in axons.
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Author details
Funding
National Institute of Neurological Disorders and Stroke (1K99NS086903)
- Catherine M Drerup
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD072844)
- Alex V Nechiporuk
OHSU Center for Spatial Systems Biomedicine (GBMEN0245A1)
- Alex V Nechiporuk
National Institute of Neurological Disorders and Stroke (F31 NS096814)
- Amy L Herbert
Philip and Seema Needleman (Graduate Student Fellowship)
- Amy L Herbert
National Multiple Sclerosis Society (Harry Weaver Scholar)
- Kelly R Monk
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations specified in the Oregon Health and Science University Guide for the Care and Use of Laboratory Animals. All animals were handled in accordance with the institutional animal care and use committee (IACUC) protocol # IS00002972.
Reviewing Editor
- Tanya T Whitfield, University of Sheffield, United Kingdom
Publication history
- Received: October 9, 2016
- Accepted: April 12, 2017
- Accepted Manuscript published: April 17, 2017 (version 1)
- Version of Record published: May 2, 2017 (version 2)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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