Impairment of serine transport across the blood-brain barrier by deletion of Slc38a5 causes developmental delay and motor dysfunction.

Brain L-serine is critical for neurodevelopment and is thought to be synthesized solely from glucose. In contrast, we found that the influx of L-serine across the blood-brain barrier (BBB) is essential for brain development. We identified the endothelial Slc38a5, previously thought to be a glutamine transporter, as an L-serine transporter expressed at the BBB in early postnatal life.

D-Serine Signaling and NMDAR-Mediated Synaptic Plasticity Are Regulated by System A-Type of Glutamine/D-Serine Dual Transporters.

D-serine is a physiologic coagonist of NMDA receptors (NMDARs) required for synaptic plasticity, but mechanisms that terminate D-serine signaling are unclear. In particular, the identity of unidirectional plasma membrane transporters that mediate D-serine reuptake has remained elusive. We report that D-serine and glutamine share the same neuronal transport system, consisting of the classic system A transporters Slc38a1 and Slc38a2.

ASCT1 (Slc1a4) transporter is a physiologic regulator of brain d-serine and neurodevelopment.

d-serine is a physiologic coagonist of NMDA receptors, but little is known about the regulation of its synthesis and synaptic turnover. The amino acid exchangers ASCT1 (Slc1a4) and ASCT2 (Slc1a5) are candidates for regulating d-serine levels. Using ASCT1 and ASCT2 KO mice, we report that ASCT1, rather than ASCT2, is a physiologic regulator of d-serine metabolism.