Characterizing unexpected interactions of a glutamine transporter inhibitor with members of the SLC1A transporter family

Abstract

The solute carrier 1A family comprises a group of membrane proteins that act as dual-function amino acid transporters and chloride (Cl−) channels and includes the alanine serine cysteine transporters (ASCTs) as well as the excitatory amino acid transporters. ASCT2 is regarded as a promising target for cancer therapy, as it can transport glutamine and other neutral amino acids into cells and is upregulated a of The is the of ASCT2 cancer the ASCT2 is and that the of ASCT2 the as a the transport is a for of the solute carrier 1A family a of that the for transport for that of the excitatory amino acid transporters. the of The solute carrier 1A family comprises a group of membrane proteins that act as dual-function amino acid transporters and chloride (Cl−) channels and includes the alanine serine cysteine transporters (ASCTs) as well as the excitatory amino acid transporters. ASCT2 is regarded as a promising target for cancer therapy, as it can transport glutamine and other neutral amino acids into cells and is upregulated a of The is the of ASCT2 cancer the ASCT2 is and that the of ASCT2 the as a the transport is a for of the solute carrier 1A family a of that the for transport for that of the excitatory amino acid transporters. the of The alanine serine cysteine transporters as and the and a neutral amino acid transport and of a neutral amino acid and of a neutral amino acid the and and ASCT2 is other transport the amino acid transporters and other glutamine transporters the family of neutral amino acid transporters transporters cells and and ASCT2 of and the of acid transporters and the and and the and for cancer and of of ASCT2 the of ASCT2 transport the amino acid glutamine the a and cancer cells as a target for cancer a that and glutamine glutamine a glutamine for and of as a target for cancer a that and glutamine glutamine of the solute carrier 1A includes the transporters as excitatory amino acid transporters The of the excitatory and amino acid transport the amino acid transporters and of the of the family as the membrane and amino acids chloride (Cl−) and of excitatory amino acid of the neutral amino acid excitatory of a chloride transporters a chloride of the the chloride (Cl−) as well as a of other that the of is a neutral amino acid chloride amino acid ASCT2 and a and of a is transport and excitatory of a chloride is a neutral amino acid chloride for the neutral amino acid ASCT2 excitatory amino acid of the family The amino acid transporters transport is the of and the of a the as of neutral amino acids amino acid ASCT2 and a the neutral amino acid the of cancer as and and as of The the as comprises that the and a of the the of a as as the of transporters and of a ASCT2 as serine and glutamine for the neutral amino acid ASCT2 glutamine as of the ASCT2 neutral amino acid as of ASCT2 the of the glutamine a acid a and of glutamine transport it that is ASCT2 and transporters of amino acid ASCT2 of the of ASCT2 the of The of of and of of the neutral amino acid transporters and of ASCT2 and of ASCT2 ASCT2 of and ASCT2 the of a cancer is the glutamine glutamine as of the ASCT2 neutral amino acid for and glutamine transport ASCT2 is and transporters a glutamine as of the ASCT2 neutral amino acid of amino acid ASCT2 for transporters and cancer the transport for neutral amino of the of of cancer of of ASCT2 of the of ASCT2 into the glutamine and it is as a as a of amino acid ASCT2 and other the the it the the of cancer cells the of the of of the membrane can membrane and and the of cancer cells channels cancer cancer is for ASCT2 into the glutamine that it other the is the family and of excitatory amino acid of the neutral amino acid and and that as of and transport and the of the of the of the the of the of and that of the transporters. and the of the of that is a of the of a and neutral amino acid transporters and ASCT2 as for neutral amino acid that the is a of neutral amino acid is a neutral amino acid chloride amino acid ASCT2 and a the neutral amino acid the amino acid neutral amino acid the of and proteins the of a of is is a neutral amino acid chloride amino acid ASCT2 and a is of a and a is a neutral amino acid chloride amino acid ASCT2 and a for the neutral amino acid ASCT2 is the and of that the of as a of of of the serine and that the the transport of of the for the neutral amino acid ASCT2 that is of the of ASCT2 and of transporters and the of the the the ASCT2 and of and cells of and of of a of membrane and of serine and a is the membrane and and as of membrane that the the of serine and the chloride (Cl−) and of serine and the of of a into the of glutamine transport into the glutamine The into a as that the can of the the of is of and and of serine for and for and and for ASCT2 transporters as the serine the for of the for of of serine for and glutamine for and for the of of alanine serine cysteine and and of for the of the of the of and of and for ASCT2 of serine the of the and as a of the of amino acid ASCT2 for transporters and cancer of and of of and of of the of glutamine the is of a is a cells and glutamine of and the of glutamine that and is a of the of glutamine ASCT2 is a of and cells the for of of serine for and for and for and of of glutamine glutamine of and a alanine serine cysteine as a of the the of that the and the membrane that a is a of the and the the of and the that the the of the that the of the is a of and of of and cells and the of of of and for of and a excitatory amino acid the of of of the of transporters that the as can and of that transport the transporters the of the the and and The the the of that that and and the the and that the is of the of of the of transport of and the of the transport that membrane and transport of of is is and the as that the the and the and is and serine and and the of and and and and of the of and other transporters well as of ASCT2 cancer The of of glutamine it can amino acid transporters the and of amino acid ASCT2 for transporters and cancer the transport for neutral amino that of amino acid is the of a family amino acid of the cancer the is The of the is as is the of transporters transporters a chloride transport the of the chloride the excitatory amino acid and of the excitatory amino acid and the of the and and of cancer and the membrane cancer channels cancer cancer is a cancer that glutamine transport the chloride as of the other the of the and the and is as a as channels chloride chloride and of that and and the for cancer that is cancer it and and of and and and The excitatory amino acid and and transport of transporters and of of the transporters and cancer of the as and of and can and and other of amino acid transporters and is a for cancer and for the glutamine the of and of cells of of the of of the and the glutamine it is that ASCT2 a is a the of into the 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neutral amino that the and of chloride the the into into cells the and the the the the and The of the and the the and as acid the the the for as the of the of for the and of for of as a and for a of a and a and a of the into a the and The of as the the and the as and for as for and for other as The a and a and the and a of the is the the and is the a the of the for of and the and the is the and is the is transporters of as a of for and and a the the as as of as a of and for the is the and is the the a the The alanine serine cysteine transporters as and the and a neutral amino acid transport and of a neutral amino acid and of a neutral amino acid the and and ASCT2 is other transport the amino acid transporters and other glutamine transporters the family of neutral amino acid transporters transporters cells and and ASCT2 of and the of acid transporters and the and and the and for cancer and of of ASCT2 the of ASCT2 transport the amino acid glutamine the a and cancer cells as a target for 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and the of the of the of the the of the of and that of the transporters. and the of the of that is a of the of a and neutral amino acid transporters and ASCT2 as for neutral amino acid that the is a of neutral amino acid is a neutral amino acid chloride amino acid ASCT2 and a the neutral amino acid the amino acid neutral amino acid the of and proteins the of a of is is a neutral amino acid chloride amino acid ASCT2 and a is of a and a is a neutral amino acid chloride amino acid ASCT2 and a for the neutral amino acid ASCT2 is the and of that the of as a of of of the serine and that the the transport of of the for the neutral amino acid ASCT2 that is of the of ASCT2 and of transporters and the of the the the ASCT2 a of membrane and of serine and a is the membrane and and as of membrane that the the of serine and the chloride (Cl−) and of serine and the of of a into the of glutamine transport into the glutamine The into a as that the can of the the of is of and and of serine for and for 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