Development of the sigma-1 receptor in C-terminals of motoneurons and colocalization with the N,N′-dimethyltryptamine forming enzyme, indole-N-methyl transferase

The function of the sigma-1 receptor (S1R) has been linked to modulating the activities of ion channels and G-protein-coupled receptors (GPCR). In the CNS, the S1R is expressed ubiquitously but is enriched in mouse motoneurons (MN), where it is localized to subsurface cisternae of cholinergic postsynaptic densities, also known as C-terminals. We found that S1R is enriched in mouse spinal MN at late stages of embryonic development when it is first visualized in the endoplasmic reticulum. S1Rs appear to concentrate at C-terminals of mouse MN only on the second week of postnatal development. We found that indole-N-methyl transferase (INMT), an enzyme that converts tryptamine into the sigma-1 ligand dimethyltryptamine (DMT), is also localized to postsynaptic sites of C-terminals in close proximity to the S1R. This close association of INMT and S1Rs suggest that DMT is synthesized locally to effectively activate S1R in MN.

▶In this study, we examined development and subcellular localization of the sigma-1 receptor (S1R) in motoneurons (MN). ▶We found that S1R is enriched in mouse spinal MN at late stages of embryonic development when it is first visualized in the endoplasmic reticulum. ▶In second postnatal week, S1Rs appear to concentrate at cholinergic postsynaptic densities (C-terminals) of MN. ▶Indole-N-methyl transferase (INMT), an enzyme that converts tryptamine into the sigma-1 ligand dimethyltryptamine (DMT), is also localized to postsynaptic sites of C-terminals. ▶This close association of INMT and S1Rs suggest that DMT is synthesized locally to effectively activate S1R in MN.