ACTR10 (Arp11), the pointed-end subunit of the dynactin complex, mediates the physical attachment of dynactin-bound cargo to the dynein retrograde motor in neurons PMID:28414272. It is specifically required for coupling mitochondria to dynactin and thereby for dynein-driven retrograde mitochondrial transport in axons; an Actr10 construct lacking its dynactin-binding domain still binds mitochondria, indicating that Actr10 functions as the mitochondria-anchoring element rather than merely a structural dynactin subunit PMID:28414272. This retrograde transport activity is essential for homeostatic mitochondrial distribution: its loss causes aged organelles to accumulate at axon terminals while cell body mitochondria are depleted PMID:33376159. Beyond mitochondria, Actr10 is required for proper distribution of Mbp mRNA in oligodendrocytes, where Mbp mRNA granules associate with the dynein/dynactin motor complex, extending its role to motor-driven mRNA transport PMID:29073112. Genetic interaction places Actr10-dependent retrograde mitochondrial movement in a pathway with the fission GTPase Drp1 PMID:28414272.
| Year | Confidence | Finding | PMIDs | Journal |
|---|---|---|---|---|
| 2017 | High | Actr10 (Arp11 subunit of dynactin) is required for dynactin-mitochondria interaction and mitochondrial retrograde transport in axons. Loss-of-function mutation in zebrafish actr10 causes failure of mitochondria to attach to the dynein retrograde motor. An Actr10 construct lacking the dynactin-binding domain retains mitochondria-binding ability, indicating Actr10 mediates dynactin-mitochondria interaction rather than simply serving as a structural dynactin subunit. | PMID:28414272 | eLife |
| 2017 | Medium | Genetic interaction studies implicated Drp1 as a partner in Actr10-dependent mitochondrial retrograde transport, placing Actr10 in a pathway with the mitochondrial fission GTPase Drp1 for retrograde axonal transport. | PMID:28414272 | eLife |
| 2017 | High | actr10 mutation in zebrafish causes failure to properly distribute mbp mRNA in oligodendrocytes, revealing a role for the Arp11/dynactin subunit in anterograde Mbp mRNA transport. Biochemical isolation of reporter-tagged Mbp mRNA granules from primary mammalian oligodendrocytes showed that they associate with the retrograde dynein/dynactin motor complex. | PMID:29073112 | Proceedings of the National Academy of Sciences of the United States of America |
| 2020 | Medium | Disruption of actr10-dependent retrograde mitochondrial transport in zebrafish neurons leads to accumulation of aged organelles in axon terminals and loss of cell body mitochondria, demonstrating that Actr10-mediated retrograde transport is essential for homeostatic mitochondrial distribution throughout the neuron. | PMID:33376159 | The Journal of neuroscience : the official journal of the Society for Neuroscience |