Regulation of mitochondrial transport in axons by nerve growth factor signaling
Abstract
The axonal transport of mitochondria responds to physiological changes in the neuron. This involves both a transition between motile and stationary states of mitochondria, and modulation of their anterograde transport activity, but the cellular signals responsible remain unknown. We report here that mitochondria accumulate in sensory axons at regions of focal stimulation with nerve growth factor (NGF) coupled to polystyrene beads. Other organelles move unimpeded through the region of the axon in contact with an NGF-bead, so this response is specific to mitochondria, and does not result from gross cytoskeletal disruption in the region of stimulation. The NGF effect on mitochondrial behavior is mediated by the Trk A receptor tyrosine kinase, and is completely eliminated by inhibitors of the phosphoinositide-3 (PI-3) kinase pathway. In axons made devoid of F-actin by latrunculin B treatment, bidirectional transport of mitochondria continues, but they can no longer accumulate in the region of NGF stimulation. We conclude that signaling events initiated by NGF-receptor binding and mediated by the PI-3 kinase pathway can regulate mitochondrial transport in neurons, and suggest that axonal mitochondria can respond to signals by undergoing docking interactions with the actin cytoskeleton.
Degree
Ph.D.
Advisors
Hollenbeck, Purdue University.
Subject Area
Cellular biology|Neurology
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