Relation of somal lipid synthesis to the fast axonal transport of protein and lipid.
The role of somal lipid synthesis in the fast axonal transport of protein and lipid was examined in vitro utilizing spinal/sciatic nerve preparations of bullfrog. Inhibition of phospholipid synthesis in dorsal root ganglia by the amphiphilic cation, fenfluramine (0.1-2.0 mM) was monitored as decreased incorporation of [3H]choline into phosphatidyl choline. This inhibition was directly proportional to a decrease in the amount of [3H]protein undergoing fast axonal transport, the two variables being related by a slope close to unity. [3H]Choline-labeled lipid undergoing fast transport in the axon was unaffected by inhibition of somal phospholipid synthesis. Levels of fenfluramine up to 1.0 mM had no effect on uptake or incorporation of [3H]leucine. Selective exposure of desheathed nerve trunks to 1.0 mM fenfluramine had no effect on [3H]protein translocation, indicating that local phospholipid synthesis is not required to maintain ongoing transport in the axon. Inhibition of cholesterol synthesis in the ganglia with the analog 20,25-diazacholesterol also resulted in depression of [3H]protein transport. Since synthesis of both phospholipid and cholesterol are required at the level of the ganglion, it is suggested that the initiation of fast axonal transport of protein is dependent on the assembly of lipoprotein structures in the soma.
D000818:Animals; D001001:Anura; D001370:Axonal Transport / Q000187:drug effects; D002746:Chlorpromazine / Q000494:pharmacology; D002794:Choline / Q000378:metabolism; D005277:Fenfluramine / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010743:Phospholipids / Q000096:biosynthesis*; D011892:Rana catesbeiana; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism
D009419:Nerve Tissue Proteins; D010743:Phospholipids; D005277:Fenfluramine; D007930:Leucine; D002794:Choline; D002746:Chlorpromazine