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J Biol Chem, Vol. 273, Issue 31, 19363-19366, July 31, 1998

COMMUNICATION
Occurrence of an Unusual Phospholipid, Phosphatidyl-L-threonine, in Cultured Hippocampal Neurons
EXOGENOUS L-SERINE IS REQUIRED FOR THE SYNTHESIS OF NEURONAL PHOSPHATIDYL-L-SERINE AND SPHINGOLIPIDS

Junya MitomaDagger §, Takeshi Kasama, Shigeki FuruyaDagger , and Yoshio HirabayashiDagger

From the Dagger  Laboratory for Cellular Glycobiology, Frontier Research Program and the § Special Postdoctoral Researchers Program, The Institute of Physical and Chemical Research (RIKEN), Wako, Saitama 351-0198, Japan and the  Instrumental Analysis Research Center for Life Science, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan

We have recently reported that L-serine released from astroglial cells supports the survival and neuritogenesis of hippocampal neurons under a serum- and glia-free culture condition (Mitoma, J., Furuya, S., and Hirabayashi, Y. (1998) Neurosci. Res. 30, 195-199). In this study, we show that exogenous L-serine is required for the synthesis of phosphatidyl-L-serine (PS) and sphingolipids in hippocampal neurons. When hippocampal neurons were maintained under an astroglial cell-free condition, the levels of sphingolipids and phosphatidyl-L-serine in the neurons were greatly reduced in the absence of external L-serine or glycine. Instead, a novel phospholipid appeared just ahead of PS on TLC. This novel lipid was determined to be phosphatidyl-L-threonine by TLC blotting/negative secondary ion mass spectrometry and amino acid analysis. Biochemical studies on rat brain microsomes have indicated that phosphatidyl-L-threonine is synthesized by the base exchange enzyme that is involved in PS synthesis with much lower affinity, that is, approximately <FR><NU>1</NU><DE>150</DE></FR> of L-serine. Addition of L-serine or glycine to the culture medium restored the synthesis of PS and sphingolipids in the neurons. These observations show that hippocampal neurons require exogenous L-serine for the synthesis of PS and sphingolipids in the absence of astroglial cells and suggested that astroglial cells contribute to neuronal lipid synthesis through the supply of L-serine.


Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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