Inhibition of Neurite Outgrowth by Overexpression of Goα

Abstract

G proteins mediate signal transductions generated by neurotransmitters and hormones.

Among G proteins, Go is found in a large quantity in brain, but its precise role in the

nervous tissue is not fully understood. In addition, Go is one of the major proteins in

growth cone membranes, which implies an important role of Go in the regulation of

axon outgrowth.

In this study, we attempted to determine the role of Go in axon outgrowth. We

overexpressed the α subunit of Go (αo) in Fl1 neuroblatoma cells and examined the

effect of αo on the neurite outgrowth. In Fl1 cells, dibutyryl CAMP increased neurite

outgrowth remarkably upto 0.1 mM in a concentration dependent manner, but in a less

degree at higher concentration. In the presence of 0.5 mM dibutyryl CAMP, the

differentiation of F11 cells was almost saturated and the cells exhibited a typical

neuronal morphology. Overexpression of αo caused a reduction of neurite outgrowth by

77.4% in length while increasing the number of neurites by 2.2 fold. The average

neurite length was 38.9±12.5 um in the αo-overexpressing Fl1 cells but 172.3±25.9 um

in the untransfected cells. The total number of nurites per cell was 5.6±0.4 in the α

o-overexpressing cells but 2.5 0.2 in the untransfected cells.

This result suggests that Go may play an important role in growth cone collapse

during neuronal cell differentiation.