Human-specific mutations in VMAT1 confer functional changes and multi-directional evolution in the regulation of monoamine circuits.

ABSTRACT:

Background

Neurochemicals like serotonin and dopamine play crucial roles in human cognitive and emotional functions. Vesicular monoamine transporter 1 (VMAT1) transports monoamine neurotransmitters, and its variant (136Thr) is associated with various psychopathological symptoms and reduced monoamine uptake relative to 136Ile. We previously showed that two human-specific amino acid substitutions (Glu130Gly and Asn136Thr/Ile) of VMAT1 were subject to positive natural selection. However, the potential functional alterations caused by these substitutions (Glu130Gly and Asn136Thr) remain unclear. To assess functional changes in VMAT1 from an evolutionary perspective, we reconstructed ancestral residues and examined the role of these substitutions in monoamine uptake in vitro using fluor

SUBMITTER: Sato DX 

PROVIDER: S-EPMC6889191 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature