Expression and regulation of 4F2hc and hLAT1 in human trophoblasts

Abstract

The neutral amino acid transport system L is a sodium-independent transport system in human placenta and choriocarcinoma cells. Recently, it was found that the heterodimer composed of hLAT1 (a light-chain protein) and 4F2 heavy chain (4F2hc), a type II transmembrane glycoprotein, is responsible for system L amino acid transport. We found that the mRNAs of 4F2hc and hLAT1 were expressed in the human placenta and a human choriocarcinoma cell line. The levels of the 4F2hc and hLAT1 proteins in the human placenta increased at full term compared with those at midtrimester. Immunohistochemical data showed that these proteins were localized mainly in the placental apical membrane. Data from leucine uptake experiments, Northern blot analysis, and immunoblot analysis showed that this transport system was partially regulated by protein kinase C and calcium ionophore in the human choriocarcinoma cell line. Our results suggest that the heterodimer of 4F2hc and hLAT1 may play an important role in placental amino acid transport system L.

Expression of thyroid hormone transporters in the human placenta and changes associated with intrauterine growth restriction

“…Patel et al [23] showed a decreased mRNA expression of OATP1A2 but no change for OATP4A1 at 9-12 wks compared to term. In accord with our findings, CD98 mRNA has been reported throughout gestation [39] and lower placental expressions of CD98 and LAT1 protein at 12-21 wks compared to term have been reported [40]. Although the presence of mRNAs encoding MCT10 and 305 LAT2 has been described in human term placenta [22,24], this is the first report of their ontogeny across gestation.…”

“…In contrast, 310 OATP4A1 protein was preferentially localised in villous syncytiotrophoblasts throughout gestation, confirming a previous report on term placenta [26]. Other studies have also reported LAT1 and CD98 expression in the syncytiotrophoblast layer at term [40,25] and LAT2 activity has been described in both the apical and basal membranes of the villous syncytiotrophoblast [41,42]. 315…”

Placental Transport of Thyroid Hormone and Iodide

“…Since this time significant findings in placental TH transporters have been made. TH transporters identified in the human placenta to date include the monocarboxylate transporters MCT8 (Chan, et al 2006) & MCT10 (Friesema, et al 2008), L-type amino acid transporters LAT1 (Okamoto, et al 2002) and LAT2 (Park, et al 2005) and organic anion transporting polypeptides OATP1A2 (Patel, et al 2003) and OATP4A1 (Patel et al 2003) (Sato, et al 2003). However, their individual contribution to placental TH transport has yet to be elucidated.…”

“…LAT1 protein has been localised to the ST layer in placenta and LAT2 to the apical and basal membranes of ST at term (Hoeltzli and Smith 1989;Lewis, et al 2007;Okamoto et al 2002;Ritchie and Taylor 2001). Localisation of the proteins throughout gestation has yet to be elucidated.…”

Expression and adaptive regulation of amino acid transport system A in a placental cell line under amino acid restriction

“…BeWo cells form a single layer on permeable supports with morphological and functional polarity (Liu et al 1997). They have previously been used in monolayer culture to study the uptake of lysine (Way et al 1998) and amino acid transport system L (Ritchie & Taylor 2001, Okamoto et al 2002 and to characterise alanine uptake (Moe et al 1994). On permeable supports they have been used to study the transepithelial transport of folic acid (Takahashi et al 2001), glucose (Vardhana & Illsley 2002) and valproic acid (Utoguchi & Audus 2000).…”