Real Time Visualization of Axonal Transport of GTPase Rab7 in Rat Embryonic Dorsal Root Ganglia

Abstract

Charcot-Marie-Tooth (CMT) neuropathy, characterized by severe sensory neuron loss, is the most common inherited disorder of the peripheral nervous system. Several GTPase Rab7 protein mutants, mainly targeted to the highly conserved amino acid, have been identified in CMT type 2B. Exact mechanism of how such point mutations cause malfunction of neurons is not well understood. Here, we studied how those Rab7 mutations affect their axonal transport in primary rat dorsal root ganglia neurons. Real time fluorescence imaging revealed that Rab7-containing endosomes engage in bi-directional transport in axons, similar to that of TrkA receptors in the same culture. However, the speed of Rab7 transport is significantly slower than that of TrkA. In addition, there is a clear variation in the speed of axonal transport between wild-type Rab7 and mutated Rab7 proteins. Our work suggested that point mutations of Rab7 proteins could potentially cause or contribute to CMT2B neurodegenerative disease by regulating its axonal transport process.