High affinity D- and L-serine transporter Asc-1: Cloning and dendritic localization in the rat brain.

Abstract

D-serine is an endogenous modulator of N-methyl-D-aspartate (NMDA)/glutamate receptors. L-serine, the precursor of D-serine, is also essential for survival and development of neurons including cerebellar Purkinje neurons. We have recently identified a high affinity D- and L-serine transporter Asc-1 from mouse and human brain. In this study, we isolated a cDNA for the rat orthologue of Asc-1, and generated two kinds of polyclonal antibodies against Asc-1 based on the amino acid sequence of rat Asc-1. Using these antibodies, we performed immunohistochemical analysis to determine the localization of Asc-1 in rat brains. Asc-1 immunoreactivity was detected in neurons, including cerebellar Purkinje neurons and pyramidal neurons in the hippocampus and the neocortical layers III and V. It was clearly localized in dendrites as well as somata. Asc-1 immunoreactivity was also detected on neurons in other regions such as the cerebellar nuclei. The localization of Asc-1 in brain suggests the significant contribution of Asc-1 to amino acid mobilization in brains including the synaptic clearance of D-serine and the neuronal uptake of L-serine. [Jpn J Physiol 54 Suppl:S86 (2004)]