Brain-specific Drp1 regulates postsynaptic endocytosis and dendrite formation independently of mitochondrial division

Kie Itoh1, Daisuke Murata1, Takashi Kato1

  • 1Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, United States.

Elife
|October 12, 2019
PubMed

Insights

Dynamin-related protein 1 isoform ABCD (Drp1ABCD) in neurons regulates postsynaptic endocytosis and neuronal structure. Loss of Drp1ABCD impacts brain development and sensorimotor gating behavior in mice.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Dynamin-related protein 1 (Drp1) is known for mitochondrial division.
  • Its functions beyond mitochondrial dynamics are not well understood.
  • Alternative splicing generates multiple Drp1 isoforms, including brain-specific Drp1ABCD.

Purpose of the Study:

  • To investigate the function of the Drp1ABCD isoform in mouse neurons.
  • To determine the role of Drp1ABCD in postsynaptic processes and neuronal morphology.
  • To explore the impact of Drp1ABCD on brain function and behavior.

Main Methods:

  • Isoform-specific knockdown using shRNA in cultured neurons.
  • Isoform-specific knockout using CRISPR/Cas9 in mouse models.
  • Analysis of dendritic spine morphology and postsynaptic endocytosis.
  • Assessment of sensorimotor gating behavior in mice.

Main Results:

  • Drp1ABCD expression is upregulated during postnatal brain development.
  • Drp1ABCD localizes to dendritic spines and regulates clathrin-mediated endocytosis independently of mitochondrial division.
  • Loss of Drp1ABCD leads to ectopic dendrite formation and altered sensorimotor gating.

Conclusions:

  • Drp1ABCD plays a critical role in postsynaptic endocytosis.
  • Drp1ABCD influences neuronal morphology and brain function.
  • This isoform is a key regulator of neuronal development and behavior.

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