Local glycolysis fuels actomyosin contraction during axonal retraction
Renata Santos1,2, Ludmilla Lokmane3, Dersu Ozdemir1
1Université Paris Cité, Institute of Psychiatry and Neuroscience of Paris, INSERM U1266, Laboratory of Dynamics of Neuronal Structure in Health and Disease, Paris, France.
The Journal of Cell Biology
|October 30, 2023
Summary
Axonal growth cone retraction relies on actomyosin contraction, fueled by glycolysis, not cellular ATP. This energy coupling occurs locally in the growth cone, impacting axonal guidance.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Axonal growth cones retract in response to repulsive cues.
- This process requires actomyosin contractility mediated by non-muscle myosin II (NMII).
- NMII generates mechanical force using ATP.
Purpose of the Study:
- To investigate the energy source for actomyosin-driven axonal retraction.
- To determine the relationship between glycolysis, actomyosin activity, and axonal guidance.
Main Methods:
- Chemical inhibition and genetic knockdown of Glyceraldehyde 3-phosphate dehydrogenase (GAPDH).
- Co-immunoprecipitation and proximal-ligation assays.
- Microfluidic experiments.
Main Results:
- Axonal retraction is dependent on ATP generation by glycolysis, independent of bulk cellular ATP levels.
- Actomyosin complexes associate with glycolytic enzymes, with enhanced association during retraction.
- Energetic coupling between glycolysis and actomyosin is localized to the growth cone and proximal axon.
Conclusions:
- Glycolysis directly fuels actomyosin contraction for axonal retraction.
- This localized energy production is crucial for growth cone guidance.
- Suggests a novel role for glycolysis in neuronal development and guidance.
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