Brain-specific Drp1 regulates postsynaptic endocytosis and dendrite formation independently of mitochondrial division.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31603426.
- Also identified by DOI 10.7554/eLife.44739 and PMC identifier 6824841.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Dynamin-related protein 1 (Drp1) divides mitochondria as a mechano-chemical GTPase. However, the function of Drp1 beyond mitochondrial division is largely unknown. Multiple Drp1 isoforms are produced through mRNA splicing. One such isoform, Drp1<sub>ABCD</sub>, contains all four alternative exons and is specifically expressed in the brain. Here, we studied the function of Drp1<sub>ABCD</sub> in mouse neurons in both culture and animal systems using isoform-specific knockdown by shRNA and isoform-specific knockout by CRISPR/Cas9. We found that the expression of Drp1<sub>ABCD</sub> is induced during postnatal brain development. Drp1<sub>ABCD</sub> is enriched in dendritic spines and regulates postsynaptic clathrin-mediated endocytosis by positioning the endocytic zone at the postsynaptic density, independently of mitochondrial division. Drp1<sub>ABCD</sub> loss promotes the formation of ectopic dendrites in neurons and enhanced sensorimotor gating behavior in mice. These data reveal that Drp1<sub>ABCD</sub> controls postsynaptic endocytosis, neuronal morphology and brain function.
Medical subject headings
- Brain
- Dendrites
- Dynamins
- Endocytosis
- Mitochondrial Dynamics
- Synapses