Retrograde Axonal Transport of the α‐Subunit of the GTP‐binding Protein G_z in Mouse Sciatic Nerve: a Potential Pathway for Signal Transduction In Neurons

Abstract

We have utilized antibodies against the alpha subunit of GZ in fluorescence immunohistochemistry to determine whether this GTP-binding protein can translocate along nerves by intra-axonal transport. After ligation of the mouse sciatic nerve we found an increase in GZ-like immunoreactivity on the proximal and distal side with time, suggesting that the alpha subunit undergoes orthograde axonal transport and also returns to the cell body by retrograde axonal transport in the sciatic nerve. Unlike the retrograde transport of Gi alpha, shown in a previous study to be present in most sciatic axons, GZ alpha only accumulated in a subpopulation of axons, suggesting that different G-proteins could convey information specific to neuronal subtypes. These results support our proposal that GZ may play a second messenger role in communicating information from the terminals back to cell bodies. Gi alpha and GZ alpha may be representative of relatively stable signalling molecules by which the signal from some neurotrophic molecules can be translocated from the neuron periphery to the cell body without the need for the retrograde transport of the neurotrophic factor itself.

A signaling organelle containing the nerve growth factor-activated receptor tyrosine kinase, TrkA

“…Our studies have identified one possible organelle that may convey the NGF signal down axons. Important signaling events may be mediated through TrkA in other organelles, through p75 NTR , or through signal transduction mediators downstream from receptors (45). Because it was the first NGF receptor to be discovered, p75 NTR was invoked in earlier versions of the ''signaling vesicle'' hypothesis (1,2).…”

Immunohistochemical expression of G protein α-subunit isoforms in rat and monkey Merkel cell-neurite complexes

“…However, Crouch et al (1994) suggested that the Gz protein is related to the signal transduction of neurotrophins, and Hendry et al (2000) recently reported that Gαz-deficient mice showed high tolerance to morphine in comparison to wild-type mice. The presence of Gz proteins in MCs may be related to the regulation of mechanoreceptive actions of the cells.…”

Structure and Function of the Pertussis-Toxin-Insensitive G_z Protein

“…Positive immunodetection of · z in dorsal root ganglion strongly supports the unique role of · z in sensory neurons [63]. Both orthograde and retrograde axonal transports of · z have been detected through ligation experiments using sensory sural nerve, sciatic nerve and dorsal root ganglion [59,63]. The retrograde axonal transport of · z targets to the nuclei of the neurons [64,65], which implies the retrograde signals carried by · z may have nuclear functions.…”

“…It is generally accepted that signaling events occurring at the synaptic end of an axon can be transmitted back to the cell body and the nucleus through retrograde axonal transport of signaling complexes. Trimeric G proteins (e.g., G i [58] and G z [59]), components of the MAP kinase cascade [60], neutrotrophic factors and their receptors [61,62] are all transported along the axons. The axonal tranport of · z is found in sciatic axons, which is distinct from the distribution of G i proteins [59].…”

“…Trimeric G proteins (e.g., G i [58] and G z [59]), components of the MAP kinase cascade [60], neutrotrophic factors and their receptors [61,62] are all transported along the axons. The axonal tranport of · z is found in sciatic axons, which is distinct from the distribution of G i proteins [59]. Positive immunodetection of · z in dorsal root ganglion strongly supports the unique role of · z in sensory neurons [63].…”