Identifying sources of D-serine in Caenorhabditis elegans and their impact on behavior

Abstract

Free D-serine (D-Ser) is a potent co-agonist of the N-methyl-D-aspartate receptor (NMDAR) in glutamate neurotransmission and regulates NMDAR functions in the nervous system. Serine racemases convert L-serine to D-Ser and are believed to be the major source of D-Ser in animals. In Caenorhabditis elegans, a knockout of the serine racemase serr-1 results in behavioral changes, but the level of D-Ser is unaffected. By growing C. elegans on peptone-free nematode growth medium (PF-NGM), we delineated the sources of D-Ser, both exogenous from peptone in culturing media and endogenous from the serine racemase serr-1, and a potential serine/aspartate racemase candidate, Y51H7C.9, identified by sequence similarity network analysis. We also discovered a new serine dehydratase (aka serine ammonia-lyase), K01C8.1, in C. elegans. We identified the serr-1 knockout and PF-NGM culturing conditions as two independent factors that impact C. elegans locomotion behavior after off-food, both short-term and long-term, and no interactions were found between the two factors.