Human ATP-binding cassette (ABC) transporter family
- PDF / 174,112 Bytes
- 10 Pages / 609.449 x 790.866 pts Page_size
- 44 Downloads / 205 Views
Human ATP-binding cassette (ABC) transporter family Vasilis Vasiliou,1 Konstandinos Vasiliou1 and Daniel W. Nebert2* 1
Molecular Toxicology and Environmental Health Sciences Program, Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO 80045, USA 2 Department of Environmental Health and Center for Environmental Genetics (CEG), University of Cincinnati Medical Center, Cincinnati, OH 45267 – 0056, USA *Correspondence to: Tel: þ1 513 821 4664; Fax: þ1 513 558 0925; E-mail: [email protected] Date received (in revised form): 23rd February 2009
Abstract There exist four fundamentally different classes of membrane-bound transport proteins: ion channels; transporters; aquaporins; and ATP-powered pumps. ATP-binding cassette (ABC) transporters are an example of ATPdependent pumps. ABC transporters are ubiquitous membrane-bound proteins, present in all prokaryotes, as well as plants, fungi, yeast and animals. These pumps can move substrates in (influx) or out (efflux) of cells. In mammals, ABC transporters are expressed predominantly in the liver, intestine, blood –brain barrier, blood – testis barrier, placenta and kidney. ABC proteins transport a number of endogenous substrates, including inorganic anions, metal ions, peptides, amino acids, sugars and a large number of hydrophobic compounds and metabolites across the plasma membrane, and also across intracellular membranes. The human genome contains 49 ABC genes, arranged in eight subfamilies and named via divergent evolution. That ABC genes are important is underscored by the fact that mutations in at least 11 of these genes are already known to cause severe inherited diseases (eg cystic fibrosis and X-linked adrenoleukodystrophy [X-ALD]). ABC transporters also participate in the movement of most drugs and their metabolites across cell surface and cellular organelle membranes; thus, defects in these genes can be important in terms of cancer therapy, pharmacokinetics and innumerable pharmacogenetic disorders. Keywords: human genome, human ATP-binding cassette (ABC) transporter gene family, genetic polymorphism, evolution, drug transport, cancer chemotherapy
Introduction Membrane transport proteins can be divided into four types: ion channels; transporters; aquaporins; and ATP-powered pumps (http://www.ncbi.nlm. nih.gov/books/bv.fcgi?rid=mcb.figgrp.4031). Genes from all four categories are ancient — with members present in most, if not all, prokaryotes, as well as in virtually all cell types of all eukaryotes. Transporters in eukaryotic cells move ions, sugars, amino acids and other molecules across all cellular and organelle membranes (cell surface, mitochondrial, endoplasmic reticulum, Golgi apparatus and
other vesicles) — with the possible exception of nuclear membranes (which have pores). The portion of the cell exposed to the lumen is called the apical surface; the rest of the cell (ie sides and base) makes up the basolateral surface. Movement of ions or other molecules into the cell is called influx; movement of ions or other molecules o
Data Loading...
