CRMP2 Is Involved in Regulation of Mitochondrial Morphology and Motility in Neurons

Tatiana Brustovetsky1, Rajesh Khanna2,3, Nickolay Brustovetsky1,4

  • 1Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Cells
|October 23, 2021
PubMed

Insights

Collapsin response mediator protein 2 (CRMP2) regulates neuronal mitochondrial dynamics. CRMP2 phosphorylation affects its binding to key proteins, influencing mitochondrial shape and movement.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Mitochondrial Dynamics

Background:

  • Mitochondrial morphology and motility are crucial for neuronal function.
  • The precise molecular mechanisms governing these processes remain largely unknown.

Purpose of the Study:

  • To investigate the role of collapsin response mediator protein 2 (CRMP2) in regulating neuronal mitochondrial morphology and motility.
  • To elucidate the impact of CRMP2 phosphorylation and its interaction with Drp1, Miro 2, and KLC1 on mitochondrial dynamics.

Main Methods:

  • Treatment of neurons with okadaic acid (OA) to induce CRMP2 and Drp1 phosphorylation.
  • Utilizing the CRMP2-binding small molecule (S)-lacosamide ((S)-LCM) to assess its effects.
  • Employing small interfering RNA (siRNA) to delete CRMP2.
  • Analyzing CRMP2 binding to Drp1, Miro 2, and KLC1.
  • Evaluating mitochondrial morphology (fission/fusion) and motility.

Main Results:

  • OA treatment increased CRMP2 and Drp1 phosphorylation, leading to reduced CRMP2 binding to Drp1, Miro 2, and KLC1.
  • (S)-LCM partially rescued CRMP2 binding and prevented OA-induced mitochondrial fission and reduced motility.
  • CRMP2 deletion via siRNA mimicked OA effects, causing increased mitochondrial fission and diminished motility.

Conclusions:

  • CRMP2 expression level and phosphorylation state are critical regulators of neuronal mitochondrial morphology and motility.
  • CRMP2's interaction with Drp1, Miro 2, and KLC1 is modulated by its phosphorylation, impacting mitochondrial dynamics.

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