The SNAT4 isoform of the system A amino acid transporter is functional in human placental microvillous plasma membrane

J Physiol. 2009 Jan 15;587(1):61-72. doi: 10.1113/jphysiol.2008.161331. Epub 2008 Nov 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Transport System A / genetics
  • Amino Acid Transport System A / metabolism*
  • Arginine / pharmacology
  • Female
  • Humans
  • Immunohistochemistry
  • In Vitro Techniques
  • Microvilli / drug effects
  • Microvilli / metabolism*
  • Molecular Sequence Data
  • Placenta / drug effects
  • Placenta / metabolism*
  • Pregnancy
  • Pregnancy Trimester, First
  • Pregnancy Trimester, Third
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • beta-Alanine / analogs & derivatives
  • beta-Alanine / metabolism


  • Amino Acid Transport System A
  • Protein Isoforms
  • RNA, Messenger
  • SLC38A1 protein, human
  • SLC38A2 protein, human
  • SLC38A4 protein, human
  • beta-Alanine
  • 2,2-dimethyl-beta-alanine
  • Arginine