Axonal Transport of the Molecular Forms of Acetylcholinesterase in Chick Sciatic Nerve

Abstract

Acetylcholinesterase (AChE) polymorphism was studied in the sciatic nerve of 4 wk old Leghorn chicks by sucrose gradient sedimentation analysis. Four main AChE molecular forms were found with sedimentation coefficients of 5S, 7.5S, 11.5S and 20S, respectively. Axonal transport of each of these forms was investigated by the enzyme accumulation kinetics measured on both sides of nerve transections and the enzyme redistribution kinetics in nerve segments isolated in vivo. After nerve transection the 11.5S and 20S forms accumulated faster in the anterograde than in the retrograde direction, and much faster than 5S and 7.5S forms in the anterograde direction. Retrograde accumulations of 5S and 7.5S were faint or negligible. By 1 h after nerve cutting the accumulation rates for 11.5S and 20S forms (but not for 5S and 7.5S) fell, in both directions, to about 1/3 of their initial values, probably due to reversal of axonal transport at the axotomy site. Local protein synthesis inhibition by cycloheximide did not affect the accumulation of 11.5S and 20S in front of a transection, at least during the 1st h, but reduced 5S and 7.5S by about 40%. In isolated nerve segments in vivo the rapidly mobile fraction of AChE constituted about 23% of the total enzyme activity present in the nerve, 14% moved in an anterograde and 9% in a retrograde direction. A small amount of 11.5S molecules (about 20%) was in rapid transit (2/3 in the anterograde and 1/3 in the retrograde direction); almost all the 20S, about 90%, migrated rapidly (2/3 forwards and 1/3 backwards). Anterograde velocities of 408 .+-. 94 and 411 .+-. 161 mm/day, respectively, were estimated for the 11.5S and 20S forms. Their respective retrograde velocities were 175 .+-. 85 and 145 .+-. 107 mm/day. If all the 5S and 7.5S molecules were moving in the anterograde direction, their accumulation rates were consistent with the average anterograde velocities of 2.9 .+-. 1.3 and 5.1 .+-. 1.4 mm/day, respectively.