Cl- absorption and HCO3- secretion are intimately associated processes vital to epithelial function, itself a key physiological activity. Until recently the transporters responsible remained obscure, but a breakthrough occurred with the discovery of the SLC26 transporters family. It is now clear that the SLC26 transporters have broad physiological functions since mutations in several members are linked to a variety of diseases. This book describes the properties of this family in detail, with contributions from the leading global researchers in the field. Complementary views from experts on other ion channels are offered in the discussions, which make fascinating reading.This family consists of at least 10 genes, each of which has several splice variants. Most members of the family are expressed in the luminal membrane of epithelial cells. Characterization of anion transport by three members has revealed that all function as Cl-/HCO3- exchangers, suggesting that SLC26 transporters are responsible for the luminal Cl-/HCO3- exchange activity. The SLC26 transporters are activated by the CF transmembrane conductance regulator and activate it in turn, leading to a model in which these molecules act together to mediate epithelial Cl- absorption and HCO3- secretion.The book includes chapters on the transport of other molecules by the SLC26 family, including oxalate in the kidney and sugars in cochlear hair cells amongst others. It also describes recent discoveries that most SLC26 transporters bind to scaffold proteins and that they all contain a conserved domain predicted to participate in protein-protein interactions. These suggest the SLC26 transporters exist in complexes with other Cl- and HCO3- transporters, and possibly other regulatory proteins. This book explores the functional role of these interactions, leading to better understanding of transepithelial fluid and electrolyte secretion and the diseases associated with it.
Author(s): Novartis Foundation
Edition: 1
Year: 2006
Language: English
Pages: 284
Cover......Page 1
Contents......Page 7
Chair’s introduction......Page 13
Overview of the SLC26 family and associated diseases......Page 14
Discussion......Page 23
Individual characteristics of members of the SLC26 family in vertebrates and their homologues in insects......Page 31
Discussion......Page 42
Sulfate transport by SLC26 transporters......Page 54
Discussion......Page 63
Sugar transport by members of the SLC26 superfamily......Page 71
Discussion......Page 80
SLC26A3 and congenital chloride diarrhoea......Page 86
Discussion......Page 98
Expression, regulation and the role of SLC26 C1/HCO exchangers in kidney and gastrointestinal tract......Page 103
Discussion......Page 115
Anion exchangers in flux: functional differences between human and mouse SLC26A6 polypeptides......Page 119
Discussion......Page 131
Physiology of electrogenic SLC26 paralogues......Page 138
Discussion......Page 150
Role of SLC26-mediated C1/base exchange in proximal tubule NaCl transport......Page 160
Discussion......Page 170
SLC26 transporters and the inhibitory control of pancreatic ductal bicarbonate secretion......Page 176
Discussion......Page 185
Regulatory interaction between CFTR and the SLC26 transporters......Page 189
Discussion......Page 198
Insights from a transgenic mouse model on the role of SLC26A2 in health and disease......Page 205
Discussion......Page 218
New insights into the role of pendrin (SLC26A4) in inner ear fluid homeostasis......Page 225
Discussion......Page 237
The renal physiology of pendrin (SLC26A4) and its role in hypertension......Page 243
Discussion......Page 251
Interaction of prestin (SLC26A5) with monovalent intracellular anions......Page 256
Discussion......Page 265
Final discussion......Page 273
Index of contributors......Page 277
Subject index......Page 279
