The phosphoinositide signaling cycle in myelin requires cooperative interaction with the axon.
Previous studies on the origin of myelin phosphoinositides involved in signaling mechanisms indicated axon to myelin transfer of phosphatidylinositol followed by myelin-localized incorporation of axon-derived phosphate groups into phosphatidylinositol 4-monophosphate and phosphatidylinositol 4,5-bisphosphate. This is in agreement with other studies showing the presence of phosphorylating activity in myelin that converts phosphatidylinositol into the mono-and diphospho derivatives. It was also found that the second messenger, inositol 1,4,5-trisphosphate, is hydrolyzed to inositol 1,4-bisphosphate by a myelin-localized enzyme. The present study was undertaken to determine the locus of the remaining reactions leading to formation of free inositol and completion of the cycle by resynthesis of phosphatidylinositol. The latter reaction was found to occur preferentially in isolated axons, and to a limited extent if at all in myelin. On the other hand, hydrolytic reactions which sequentially convert inositol 1,4,5-trisphosphate to inositol 1,4-bisphosphate, inositol 1-phosphate, and free inositol were found to occur more prominently in myelin. Thus, restoration of phosphoinositides following signal-induced breakdown of PIP2 in myelin is seen as requiring metabolic interplay between myelin and axon.
Chakraborty
G
G
Department of Neurosciences, New Jersey Medical School, UMDNJ, Newark 07103, USA.
Drivas
A
A
Ledeen
R
R
D000818:Animals; D001369:Axons / Q000378:metabolism*; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D006868:Hydrolysis; D008297:Male; D009186:Myelin Sheath / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000201:enzymology / Q000378:metabolism