title: The SNAT4 isoform of the system A amino acid transporter is functional in human placental microvillous plasma membrane.
abstract: Placental system A activity is important for the supply of neutral amino acids needed for fetal growth. There are three system A isoforms: SNAT1, SNAT2 and SNAT4, but the contribution of each to system A-mediated transport is unknown. Here, we have used immunohistochemistry to demonstrate that all three isoforms are present in the syncytiotrophoblast suggesting each plays a role in amino acid transport across the placenta. We next tested the hypothesis that the SNAT4 isoform is functional in microvillous plasma membrane vesicles (MVM) from normal human placenta using a method which exploits the unique property of SNAT4 to transport both cationic amino acids as well as the system A-specific substrate MeAIB. The data show that SNAT4 contribution to system A-specific amino acid transport across MVM is higher in first trimester placenta compared to term (approx. 70% and 33%, respectively, P < 0.01). Further experiments performed under more physiological conditions using intact placental villous fragments suggest a contribution of SNAT4 to system A activity in first trimester placenta but minimal contribution at term. In agreement, Western blotting revealed that SNAT4 protein expression is higher in first trimester MVM compared to term (P < 0.05). This study provides the first evidence of SNAT4 activity in human placenta and demonstrates the contribution of SNAT4 to system A-mediated transport decreases between first trimester and term: our data lead us to speculate that at later stages of gestation SNAT1 and/or SNAT2 are more important for the supply of amino acids required for normal fetal growth.
authors.affiliation: Maternal and Fetal Health Research Group, University of Manchester, St Mary's Hospital, Hathersage Road, Manchester M13 0JH, UK. michelle.desforges@manchester.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Desforges
authors.forename: K J
authors.initials: KJ
authors.lastname: Mynett
authors.forename: R L
authors.initials: RL
authors.lastname: Jones
authors.forename: S L
authors.initials: SL
authors.lastname: Greenwood
authors.forename: M
authors.initials: M
authors.lastname: Westwood
authors.forename: C P
authors.initials: CP
authors.lastname: Sibley
authors.forename: J D
authors.initials: JD
authors.lastname: Glazier
mesh_terms: D000595:Amino Acid Sequence; D026924:Amino Acid Transport System A / Q000235:genetics / Q000378:metabolism*; D001120:Arginine / Q000494:pharmacology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011263:Pregnancy Trimester, Third; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D026924:Amino Acid Transport System A; D020033:Protein Isoforms; D012333:RNA, Messenger; C445761:SLC38A1 protein, human; C498797:SLC38A2 protein, human; C507352:SLC38A4 protein, human; D015091:beta-Alanine; C012924:2,2-dimethyl-beta-alanine; D001120:Arginine