Identification of LAT4, a Novel Amino Acid Transporter with System L Activity

Abstract

System L amino acid transporters mediate the movement of bulky neutral amino acids across cell membranes. Until now three proteins that induce system L activity have been identified: LAT1, LAT2, and LAT3. The former two proteins belong to the solute carrier family 7 (SLC7), whereas the latter belongs to SLC43. In the present study we present a new cDNA, designated LAT4, which also mediates system L activity when expressed in Xenopus laevis oocytes. Human LAT4 exhibits 57% identity to human LAT3. Like LAT3, the amino acid transport activity induced by LAT4 is sodium-, chloride- and pH-independent, is not trans-stimulated, and shows two The of LAT4 induced activity is to the not that in LAT4 of the to to LAT4 activity is the of In that LAT4 is to the of the and the in the In the LAT4 is present in the of the System L amino acid transporters mediate the movement of bulky neutral amino acids across cell membranes. Until now three proteins that induce system L activity have been identified: LAT1, LAT2, and LAT3. The former two proteins belong to the solute carrier family 7 (SLC7), whereas the latter belongs to SLC43. In the present study we present a new cDNA, designated LAT4, which also mediates system L activity when expressed in Xenopus laevis oocytes. Human LAT4 exhibits 57% identity to human LAT3. Like LAT3, the amino acid transport activity induced by LAT4 is sodium-, chloride- and pH-independent, is not trans-stimulated, and shows two The of LAT4 induced activity is to the not that in LAT4 of the to to LAT4 activity is the of In that LAT4 is to the of the and the in the In the LAT4 is present in the of the System L is a amino acid transport system that mediates transport of neutral amino acids System L in a transport system neutral amino acids that is by a amino acid amino acid solute carrier amino acid solute carrier two system L in and transport in and and transporters system L have been the The transporters system L activity and LAT2, which of the 7 family of transporters mediate amino acid and a of neutral amino acids to neutral amino acids in the of proteins a the of a the of and the the of amino acid transporters and LAT2, of the of system of system to by the cell expressed in Xenopus system transport and is the transporters and not to transport activity the exhibits a and is to a and a whereas and in of expressed in and System L of have been in that not that system L in In the present by to LAT3, we have activity is to LAT3, LAT4 a to the of The amino acid to the The of and and The a of and human LAT4, and and by the and the The in the and the of LAT4 the human LAT4 a to by cell the in study in the The and and Xenopus laevis human LAT4, human human of and Xenopus human the of amino acids The the amino acid and amino acid and of three the amino acid by in The to in LAT4 in amino in the in the of amino acids in the of the and human a the LAT4 of the in by in a to a by in and in and and in of the a a activity of the human and the the system the in and the in in a and to a the to to LAT1, LAT2, LAT3, and LAT4 and in a by by of a LAT4 a human LAT4 the in a and and in Human in a in and in and to the by to to and and the the of in a of and and by and transport the the in The of by System transport when in in and by in and in and of the of the the to the the amino and when by the and three to and in of and to the to the in a and to the in in three in in in and in in in the The The three in in The a a the of and and proteins and to membranes. The in and the by in that the in and to the of been a new that mediates system L amino acid transport activity is expressed in and the of proteins that mediate activity in shows a of identity two human the and the Human LAT4 a a acid a of The a and the to the The a of that a LAT4 a 57% identity to and identity to In we have LAT4 LAT4 is to human that LAT3, LAT4, and belong to the family LAT4 to proteins system L transport activity and to of the and of of proteins the and The a in the and the that the the two in in LAT4 a and the is we the and by in whereas a in that LAT4 the and that the of LAT4 is not In the LAT4 in amino acid not we not which is a and is of In the to the that LAT4 is amino acid we the of amino acids in human LAT4 of and when LAT4 and LAT4 also induced transport when expressed in not transport is not sodium-, and of LAT4 in laevis oocytes. the the of amino acids and of the transport induced by LAT4 in a of in acid by the of the that of the to a of three the induced transport activity of and and and to the of LAT4 in to the of a transport activity two The a of and and the a of and of transport LAT4 the the of in the of The transport activity in that of oocytes. to a The and The shows the of the in a new the activity induced by LAT4, we the of by amino acids a and amino acids not the neutral amino acids LAT4, which of the of In and of The system amino acid also the of that the activity induced by LAT4 to system transport of oocytes. of LAT4 the of in the of in the in the of the amino acids amino acid to in to transport The in the and LAT4 and and LAT4 and the of the amino acid transport in the of and the induced transport transport of to that of LAT4 to in which a is to amino of LAT4 the in and in and The of the of the in amino acid in of the and of the the to the of to a three of three and expressed of the we the amino acid activity is of and by the in to and which have a of a also the of a is a of LAT4 the of and the of the amino acid by the to the amino The of of the amino acid in the of acid the in that the the the of LAT4 transport activity been to to the to the transporters a system to to a is to and LAT4 and is the system L the of LAT4, the of the activity by the to in a of the of transport of transport of system L of the of in to a and of of LAT4 the the of in not The transport activity in that in oocytes. to a in a of LAT4 in which been by to and to oocytes. The in the LAT4 the in the and 7 is that in the of LAT3. in LAT4 is in the three proteins of the family in that of have the activity of the of to in a of the transport activity the to we the of the activity of the activity of to of LAT4 the to and the of LAT4 in human and The two of and of in human and Human LAT4 in in and LAT4 is expressed in In to in human a and human and LAT4 in that of transporters in human and a human The a of the human and in Human to of and and cell by in to a and to a LAT4 in to a of and The to the in of LAT4 in and not whereas the system L LAT1, is also expressed in we the of a activity in in to of two a a of and a of of and a a of and a of study the we is a transport activity that is not by a is by a the in In that the to in in of the the the in that the to and activity in the and the to and of the in and LAT4, and in to the and to and the and the and the and and the LAT4 in and to transport in the of The and The shows the of the to of three of a of of in the of the The by is not of three of a and activity of of the of the of transport in and the transport of to of of the in study which in and LAT4, we in in of and in human In the human and not LAT4 in of the and in the the In the the expressed in of the and in the of the in the human LAT4 in LAT4 in the of the of of human and and and and LAT4 of two in the LAT4 is to the and the is in the the in the the to and is a in the of the in the and LAT4 in the of the and and the of to the we have a new amino acid system L transport activity LAT4 and identity to of of we that and LAT4 a new family of solute transporters that also the that proteins to of the family to of the family and to of the amino acid transport family and and LAT2, LAT4 amino acid transport activity in we not of amino acid transport activity in oocytes. to that a and LAT4 and a of and to the amino acid and of the by in the the of two transporters the of activity that of in new family of transporters is the LAT4, the is to been that the of In the present study we that of a in the family in a transport activity to is in a in the of the of the activity and that of that the to of in LAT4 not to have the is to L in the and by and and in the and have been in cell and that of the and been in by system is by and System is to by whereas system is not the transport and the of and the of to the to LAT3, LAT4 to activity in of LAT4 in the study of a activity in the study of transporters the and have a activity the that a the of a to transport and is to that LAT4 have in the of the cell to the of the cell to the of amino the the of in the of the of amino acids a of LAT4 in of amino of amino acids been and in the of the a in the of LAT4 is expressed in and to the of neutral amino acids and In the LAT4 is expressed in the a in the of bulky neutral amino acid transport have been in and LAT4 also in the to LAT4 is transport human LAT4 is expressed in a the of the of is the of the activity in The of a activity the of and the of LAT4 that LAT4 In the of the of amino acids and to the amino acid to the of in and in to the and of LAT4 the not by the of the activity of LAT4 the to the of System L is a amino acid transport system that mediates transport of neutral amino acids System L in a transport system neutral amino acids that is by a amino acid amino acid solute carrier amino acid solute carrier two system L in and transport in and and transporters system L have been the The transporters system L activity and LAT2, which of the 7 family of transporters mediate amino acid and a of neutral amino acids to neutral amino acids in the of proteins a the of a the of and the the of amino acid transporters and LAT2, of the of system of system to by the cell expressed in Xenopus system transport and is the transporters and not to transport activity the exhibits a and is to a and a whereas and in The of expressed in and System L of have been in that not that system L in In the present by to LAT3, we have activity is to LAT3, LAT4 a to the of The amino acid to the The of and and The a of and human LAT4, and and by the and the The in the and the of LAT4 the human LAT4 a to by cell the in study in the The and and Xenopus laevis human LAT4, human human of and Xenopus human the of amino acids The the amino acid and amino acid and of three the amino acid by in The to in LAT4 in amino in the in the of amino acids in the of the and human a the LAT4 of the in by in a to a by in and in and and in of the a a activity of the human and the the system the in and the in in a and to a the to to LAT1, LAT2, LAT3, and LAT4 and in a by by of a LAT4 a human LAT4 the in a and and in Human in a in and in and to the by to to and and the the of in a of and and by and transport the the in The of by System transport when in in and by in and in and of the of the the to the the amino and when by the and three to and in of and to the to the in a and to the in in three in in in and in in in the The The three in in The a a the of and and proteins and to membranes. The in and the by in that the in and to the to the of The amino acid to the The of and and The a of and human LAT4, and and by the and the The in the and the of LAT4 the human LAT4 a to by cell the in study in the The and and Xenopus laevis human LAT4, human human of and Xenopus human the of amino acids The the amino acid and amino acid and of three the amino acid by in The to in LAT4 in amino in the in the of amino acids in the of the and human a the LAT4 of the in by in a to a by in and in and and in of the a a activity of the human and the the system the in and the in in a and to a the to to LAT1, LAT2, LAT3, and LAT4 and in a by In by of a LAT4 a human LAT4 the in a and and in Human in a in and in and to the by to to and and the the of in a of and and by and transport the the in The of by System transport when in in and by in and in and of the of the the to the the amino and when by the and three to and in of and to the to the in a and to the in in three in in in and in in in the The The three in in The a a the of and and proteins and to membranes. The in and the by in that the in and to the of been a new that mediates system L amino acid transport activity is expressed in and the of proteins that mediate activity in shows a of identity two human the and the Human LAT4 a a acid a of The a and the to the The a of that a LAT4 a 57% identity to and identity to In we have LAT4 LAT4 is to human that LAT3, LAT4, and belong to the family LAT4 to proteins system L transport activity and to of the and of of proteins the and The a in the and the that the the two in in LAT4 a and the is we the and by in whereas a in that LAT4 the and that the of LAT4 is not In the LAT4 in amino acid not we not which is a and is of In the to the that LAT4 is amino acid we the of amino acids in human LAT4 of and when LAT4 and LAT4 also induced transport when expressed in not transport is not sodium-, and the induced transport activity of and and and to the of LAT4 in to the of a transport activity two The a of and and the a of and of transport LAT4 the the of in the of The transport activity in that of oocytes. to a The and The shows the of the in a new the activity induced by LAT4, we the of by amino acids a and amino acids not the neutral amino acids LAT4, which of the of In and of The system amino acid also the of that the activity induced by LAT4 to system transport of oocytes. of LAT4 the of in the of in the in the of the amino acids amino acid to in to transport The in the and LAT4 and and LAT4 and the of the amino acid transport in the of and the induced transport transport of to that of LAT4 to in which a is to amino of LAT4 the in and in and The of the of the in amino acid in of the and of the the to the of to a three of three and expressed of the we the amino acid activity is of and by the in to and which have a of a also the of a is a of LAT4 the of and the of the amino acid by the to the amino The of of the amino acid in the of acid the in that the the the of LAT4 transport activity been to to the to the transporters a system to to a is to and LAT4 and is the system L the of LAT4, the of the activity by the to in a of the of transport of transport of system L of the of in to a and of of LAT4 the the of in not The transport activity in that in oocytes. to a in a of LAT4 in which been by to and to oocytes. The in the LAT4 the in the and 7 is that in the of LAT3. in LAT4 is in the three proteins of the family in that of have the activity of the of to in a of the transport activity the to we the of the activity of the activity of to of LAT4 the to and the of LAT4 in human and The two of and of in human and Human LAT4 in in and LAT4 is expressed in In to in human a and human and LAT4 in that of transporters in human and a human The a of the human and in Human to of and and cell by in to a and to a LAT4 in to a of and The to the in of LAT4 in and not whereas the system L LAT1, is also expressed in we the of a activity in in to of two a a of and a of of and a a of and a of study the we is a transport activity that is not by a is by a the in In that the to in in of the the the in that the to and activity in the and the to and of the in and LAT4, and in to the and to and the and the and the and and the LAT4 in and to transport in the of The and The shows the of the to of three of a of of in the of the The by is not of three of a and activity of of the of the of transport in and the transport of to of of the in study which in and LAT4, we in in of and in human In the human and not LAT4 in of the and in the the In the the expressed in of the and in the of the in the human LAT4 in LAT4 in the of the of of human and and and and LAT4 of two in the LAT4 is to the and the is in the the in the the to and is a in the of the in the and LAT4 in the of the and and of been a new that mediates system L amino acid transport activity is expressed in and the of proteins that mediate activity in shows a of identity two human the and the Human LAT4 a a acid a of The a and the to the The a of that a LAT4 a 57% identity to and identity to In we have LAT4 LAT4 is to human that LAT3, LAT4, and belong to the family LAT4 to proteins system L transport activity and to of the and of The of proteins the and The a in the and the that the the two in in LAT4 a and the is we the and by in whereas a in that LAT4 the and that the of LAT4 is not In the LAT4 in amino acid not we not which is a and is of In the to the that LAT4 is amino acid we the of amino acids in human LAT4 of and when LAT4 and LAT4 also induced transport when expressed in not transport is not sodium-, and the induced transport activity of and and and to the of LAT4 in to the of a transport activity two The a of and and the a of and the activity induced by LAT4, we the of by amino acids a and amino acids not the neutral amino acids LAT4, which of the of In and of The system amino acid also the of that the activity induced by LAT4 to system In we the amino acid activity is of and by the in to and which have a of a also the of a is a of LAT4 the of and the of the amino acid by the to the amino The of of the amino acid in the of acid the in that the the the of LAT4 transport activity been to to the to the transporters a system to to a is to and LAT4 and is the system L the of LAT4, the of the activity by the to in a of the of transport that in the of LAT3. in LAT4 is in the three proteins of the family in that of have the activity of the of to in a of the transport activity the to we the of the activity of the activity of to of LAT4 the to and the of LAT4 in human and The two of and of in human and Human LAT4 in in and LAT4 is expressed in In to in human a and human and LAT4 in that of transporters of LAT4 in and not whereas the system L LAT1, is also expressed in we the of a activity in in to of two a a of and a of of and a a of and a of study the we is a transport activity that is not by a is by a the in In that the to in in of the the the in that the to study which in and LAT4, we in in of and in human In the human and not LAT4 in of the and in the the In the the expressed in of the and in the of the in the human LAT4 in LAT4 in the of the the of to the we have a new amino acid system L transport activity LAT4 and identity to of of we that and LAT4 a new family of solute transporters that also the that proteins to of the family to of the family and to of the amino acid transport family and and LAT2, LAT4 amino acid transport activity in we not of amino acid transport activity in oocytes. to that a and LAT4 and a of and to the amino acid and of the by in the the of two transporters the of activity that of in new family of transporters is the LAT4, the is to been that the of In the present study we that of a in the family in a transport activity to is in a in the of the of the activity and that of that the to of in LAT4 not to have the is to L in the and by and and in the and have been in cell and that of the and been in by system is by and System is to by whereas system is not the transport and the of and the of to the to LAT3, LAT4 to activity in of LAT4 in the study of a activity in the study of transporters the and have a activity the that a the of a to transport and is to that LAT4 have in the of the cell to the of the cell to the of amino the the of in the of the of amino acids a of LAT4 in of amino of amino acids been and in the of the a in the of LAT4 is expressed in and to the of neutral amino acids and In the LAT4 is expressed in the a in the of bulky neutral amino acid transport have been in and LAT4 also in the to LAT4 is transport human LAT4 is expressed in a the of the of is the of the activity in The of a activity the of and the of LAT4 that LAT4 In the of the of amino acids and to the amino acid to the of in and in to the and of LAT4 the not by the of the activity of LAT4 the to the of the of to the we have a new amino acid system L transport activity LAT4 and identity to of of we that and LAT4 a new family of solute transporters that also the that proteins to of the family to of the family and to of the amino acid transport family and and LAT2, LAT4 amino acid transport activity in we not of amino acid transport activity in oocytes. to that a and LAT4 and a of and to the amino acid and of the by in the the of two transporters the of activity that of in new family of transporters is the LAT4, the is to been that the of In the present study we that of a in the family in a transport activity to is in a in the of the of the activity and that of that the to of in LAT4 not to have the is to System L in the and by and and in the and have been in cell and that of the and been in by system is by and System is to by whereas system is not the transport and the of and the of to the to LAT3, LAT4 to activity in The of LAT4 in the study of a activity in the study of transporters the and have a activity the that a the of a to transport and is to that LAT4 have in the of the cell to the of the cell to the of amino In the the of in the of the of amino acids a of LAT4 in of amino of amino acids been and in the of the a in the of LAT4 is expressed in and to the of neutral amino acids and In the LAT4 is expressed in the a in the of bulky neutral amino acid transport have been in and LAT4 also in the to LAT4 is transport human LAT4 is expressed in a the of the of is the of the activity in The of a activity the of and the of LAT4 that LAT4 In the of the of amino acids and to the amino acid to the of in and in to the and of LAT4 the not by the of the activity of LAT4 the to the of and and and the of the the