The ABCs of membrane transporters in health and disease (SLC series): introduction

Abstract

The field of transport biology has steadily grown over the past decade and is now recognized as playing an important role in manifestation and treatment of disease. The SLC (solute carrier) gene series has grown to now include 52 families and 395 transporter genes in the human genome. A list of these genes can be found at the HUGO Gene Nomenclature Committee (HGNC) website (see www.genenames.org/genefamilies/SLC). This special issue features mini-reviews for each of these SLC families written by the experts in each field. The existing online resource for solute carriers, the Bioparadigms SLC Tables (www.bioparadigms.org), has been updated and significantly extended with additional information and cross-links to other relevant databases, and the nomenclature used in this database has been validated and approved by the HGNC. In addition, the Bioparadigms SLC Tables functionality has been improved to allow easier access by the scientific community. This introduction includes: an overview of all known SLC and "non-SLC" transporter genes; a list of transporters of water soluble vitamins; a summary of recent progress in the structure determination of transporters (including GLUT1/SLC2A1); roles of transporters in human diseases and roles in drug approval and pharmaceutical perspectives.

Fig. 1

Cartoon showing a cell with SLC and non-SLC transporters expressed in the plasma membrane or in intracellular compartments. Note that the non-SLC transporters are also expressed in intracellular compartments.

Fig. 2

Pie chart depicting the proportion of genes encoding transporter-related proteins (total number: 826). SLC = solute carrier; VGIC = voltage gated ion channels; LGIC = ligand gated ion channels; OIC = other ion channels (e.g. aquaporins, connexins); ABC = ABC transporters; P-ATPases = P-type ATPases; V-ATPases = V-type ATPases; F-ATPases = F-type ATPases.

Fig. 3

SLC family member crystal structures published since 2002. The histogram depicts the exponential evolution of the number of SLC family member crystal structures published in the last 10 years. The graph is based on information obtained from this SLC mini-review series.

Fig. 4

Crystal structure of XylE bound to d-xylose. (A) Three different views of cartoon representations and surface modeling of XylE in complex with d-xylose (PDB ID: 4GBY) by PyMOL v0.99 software. The structure of this bacterial homologue is divided into two distinct protomers (N- and C-domain) colored in orange and silver, respectively. Both domains are connected by an intracellular domain represented in gray. (B) Cartoon representation of XylE bound to d-xylose. Important transmembrane segments (TMs) involved in the binding site are colored (above, see legends). The binding site is formed by amino acids F24 (TM1), Q168 (TM5), Q288/Q289/N294/Y298 (TM7), N325 (TM8), W392 (TM10) and Q415/W416 (TM11), represented as sticks. The hydrogen bonds are depicted as dotted gray lines (below).