The Role of Rac1 in the Growth Cone Dynamics and Force Generation of DRG Neurons

PloS One
Wasim A SayyadVincent Torre

Abstract

We used optical tweezers, video imaging, immunocytochemistry and a variety of inhibitors to analyze the role of Rac1 in the motility and force generation of lamellipodia and filopodia from developing growth cones of isolated Dorsal Root Ganglia neurons. When the activity of Rac1 was inhibited by the drug EHop-016, the period of lamellipodia protrusion/retraction cycles increased and the lamellipodia retrograde flow rate decreased; moreover, the axial force exerted by lamellipodia was reduced dramatically. Inhibition of Arp2/3 by a moderate amount of the drug CK-548 caused a transient retraction of lamellipodia followed by a complete recovery of their usual motility. This recovery was abolished by the concomitant inhibition of Rac1. The filopodia length increased upon inhibition of both Rac1 and Arp2/3, but the speed of filopodia protrusion increased when Rac1 was inhibited and decreased instead when Arp2/3 was inhibited. These results suggest that Rac1 acts as a switch that activates upon inhibition of Arp2/3. Rac1 also controls the filopodia dynamics necessary to explore the environment.

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Citations

Dec 30, 2016·Developmental Neurobiology·John K Chilton, Sarah Guthrie
Apr 17, 2021·Journal of Chemical Information and Modeling·Jing XuAlessandra Magistrato
Aug 28, 2021·Biomolecules·Cian D'Arcy, Christina Kiel

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Methods Mentioned

BETA
GTPase
Optical Tweezers
GTPases
nucleotide exchange
Optical
force measurements
ELISA
Protein Assay

Software Mentioned

Xcellence
Imagej Image processing and analysis
Kymograph

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