A guide to plasma membrane solute carrier proteins

Abstract

This review aims to serve as an introduction to the solute carrier proteins (SLC) superfamily of transporter proteins and their roles in human cells. The SLC superfamily currently includes 458 transport proteins in 65 families that carry a wide variety of substances across cellular membranes. While members of this superfamily are found throughout cellular organelles, this review focuses on transporters expressed at the plasma membrane. At the cell surface, SLC proteins may be viewed as gatekeepers of the cellular milieu, dynamically responding to different metabolic states. With altered metabolism being one of the hallmarks of cancer, we also briefly review the roles that surface SLC proteins play in the development and progression of cancer through their influence on regulating metabolism and environmental conditions.

Keywords: amino acids; cancer; cell surface; cellular metabolism; cellular transport; glucose; pH; physiology; plasma membrane; solute carrier transporter.

Fig. 1

Examples of SLC proteins transporting sugars (SLC2 and SLC5). SLC2A1 is shown as an example of the SLC2 GLUT transporters, while SLC5A1 is shown as an example of the Na⁺‐dependent SLC5 family of sugar transporters.

Fig. 2

Examples of SLC proteins transporting amino acids and peptides (SLC1, SLC3, SLC6, SLC7, SLC38, and SLC43). SLC1A1 represents the SLC1 subfamily of high‐affinity glutamate transporters, while SLC1A5 represents the subfamily of neutral amino acid transporters. SLC7A1 represents the subfamily of L‐type amino acid transporters (LATs), while LAT1 represents the group of heterodimeric transporters called heteromeric amino acid transporters (HATs). SLC6A1 represents the SLC6 subfamily of GABA transporters. SLC6A2 represents the subfamily of monoamine transporters. SLC6A5 represents the subfamily of Na⁺‐ and Cl⁻‐dependent amino acid transporters while SLC6A19 represents the nutrient amino acid transporters. SLC38A1 is shown as an example of SLC38 amino acid transporter, while SLC43A1 is shown as an example of the SLC43 family of system L amino acid transporters.

Fig. 3

(A) Examples of SLC proteins transporting vitamins (SLC19 and SLC46). SLC19A1 is the folate transporter, while SLC19A2 represents the thiamine transporters. SLC46A1 is a functionally related protein that drives the absorption of folate. (B) Examples of SLC proteins transporting nucleotides and nucleosides (SLC28 and 29). SLC28A1 is shown as an example of a concentrative nucleoside transporter (CNT), while SLC29A1 is shown as an example of an equilibrative nucleoside transporter (ENT).

Fig. 4

(A) Examples of SLC proteins transporting protons and bicarbonate ions (SLC4, SLC9, SLC26). SLC4A1 represents the subfamily of anion exchangers (AE), SLC4A4 represents the subfamily of electrogenic Na⁺/HCO₃ ⁻ cotransporters, while SLC4A7 represents the subfamily of electroneutral Na/HCO₃ ⁻ cotransporters. SLC9A1 serves as the prototypical Na⁺/H⁺ exchanger. SLC26A1 is an example of an SLC26 transporter that cotransports sulfate with Cl⁻. (B) Examples of SLC proteins transporting divalent ions (SLC8 and SLC24). SLC8A1 is shown as an example of a Ca²⁺/Na⁺ exchanger. SLC24A1 is shown as an example of K⁺‐dependent Na⁺/Ca²⁺ exchangers.

Fig. 5

(A) Examples of SLC proteins transporting inorganic ions (SLC12). SLC12A1 represents the subfamily of Na⁺‐dependent cation‐Cl⁻ cotransporters (NCC), while SLC12A4 represents the subfamily of Na⁺‐independent cation‐ Cl⁻ cotransporters (KCC). (B) Examples of SLC proteins transporting carboxylates (SLC13, and SLC16). SLC13A1 represents the subfamily of Na⁺‐dependent sulfate transporters (NaS), while SLC13A5 represents the subfamily of Na⁺‐dependent di‐ and tricarboxylate transporters (NaDC). SLC16A1 is shown as an example of a monocarboxylate transporter (MCT).

Fig. 6

(A) Examples of SLC proteins transporting phosphate (SLC20 and SLC34). SLC20A1 is shown as an example of a Na⁺‐dependent transporter of inorganic phosphate (P_i). SLC34A1 represents the subfamily of electrogenic Na⁺‐dependent phosphate transporter, while SLC34A3 is the electroneutral Na⁺‐dependent phosphate transporter. (B) Examples of SLC proteins transporting organic ions (SLC14 and SLC22). SLC14A1 is shown as an example of the SLC14 family of urea transporters. SLC22A6 represents the organic anion transporter (OAT) major clade of SLC22 proteins, while SLC22A1 represents the organic cation transporter (OCT) major clade of proteins.

Fig. 7

Examples of SLC proteins transporting trace metals (SLC11, SLC30, SLC31, SLC39, SLC40, SLC41, and SLC49). SLC11A2 is shown as an example of a proton‐dependent transporter of metal ions (primarily Fe²⁺). SLC40A1 is an iron exporter. SLC39A1 is shown as an example of a zinc importer, while SLC30A1 is shown as a zinc exporter. SLC31A1 is shown as an example of a cooper transporter. SLC41A1 is shown as an example of a magnesium transporter. SLC49A1 is shown as an example of a heme transporter.

Fig. 8

Examples of SLC proteins transporting other organic compounds (SLC10 and SLCO). SLC10A1 is shown as an example of the SLC10 family that transports conjugated bile acids. SLCO1A2 represents the OATP1 subfamily and transports organic anions like bile acids. SLCO2A1 represents the OATP2 subfamily and transports prostaglandins. SLCO3A1 is the only member of the OATP3 subfamily and functions primarily as a bile acid transporter. SLCO4A1 represents the OATP4 subfamily and transports various organic compounds like prostaglandins.