The Heavy Chain 4F2hc Modulates the Substrate Affinity and Specificity of the Light Chains LAT1 and LAT2.

Kantipudi, Satish; Jeckelmann, Jean-Marc; Ucurum, Zöhre; Bosshart, Patrick D.; Fotiadis, Dimitrios (2020). The Heavy Chain 4F2hc Modulates the Substrate Affinity and Specificity of the Light Chains LAT1 and LAT2. International journal of molecular sciences, 21(20) MDPI 10.3390/ijms21207573

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The human L-type amino acid transporters LAT1 and LAT2 mediate the transport of amino acids and amino acid derivatives across plasma membranes in a sodium-independent, obligatory antiport mode. In mammalian cells, LAT1 and LAT2 associate with the type-II membrane N-glycoprotein 4F2hc to form heteromeric amino acid transporters (HATs). The glycosylated ancillary protein 4F2hc is known to be important for successful trafficking of the unglycosylated transporters to the plasma membrane. The heavy (i.e., 4F2hc) and light (i.e., LAT1 and LAT2) chains belong to the solute carrier (SLC) families SLC3 and SLC7, and are covalently linked by a conserved disulfide bridge. Overexpression, absence, or malfunction of certain HATs is associated with human diseases and HATs are therefore considered therapeutic targets. Here, we present a comparative, functional characterization of the HATs 4F2hc-LAT1 and 4F2hc-LAT2, and their light chains LAT1 and LAT2. For this purpose, the HATs and the light chains were expressed in the methylotrophic yeast Pichia pastoris and a radiolabel transport assay was established. Importantly and in contrast to mammalian cells, P. pastoris has proven useful as eukaryotic expression system to successfully express human LAT1 and LAT2 in the plasma membrane without the requirement of co-expressed trafficking chaperone 4F2hc. Our results show a novel function of the heavy chain 4F2hc that impacts transport by modulating the substrate affinity and specificity of corresponding LATs. In addition, the presented data confirm that the light chains LAT1 and LAT2 constitute the substrate-transporting subunits of the HATs, and that light chains are also functional in the absence of the ancillary protein 4F2hc.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Faculty Institutions > NCCR TransCure
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Kantipudi, Satish; Jeckelmann, Jean-Marc; Ucurum Fotiadis, Zöhre; Bosshart, Patrick and Fotiadis, Dimitrios José


500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health








Barbara Franziska Järmann-Bangerter

Date Deposited:

20 Jan 2021 17:00

Last Modified:

05 Dec 2022 15:44

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

4F2hc LAT1 LAT2 amino acid transporter heterodimeric amino acid transporter solute carrier 3 family solute carrier 7 family




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