Borate Transporters and SLC4 Bicarbonate Transporters Share Key Functional Properties.

Borate transporters are membrane transport proteins that regulate intracellular borate levels. In plants, borate is a micronutrient essential for growth but is toxic in excess, while in yeast, borate is unnecessary for growth and borate export confers tolerance. Borate transporters share structural homology with human bicarbonate transporters in the SLC4 family despite low sequence identity and differences in transported solutes. Here, we characterize the S. cerevisiae borate transporter Bor1p and examine whether key biochemical features of SLC4 transporters extend to borate transporters. We show that borate transporters and SLC4 transporters share multiple properties, including lipid-promoted dimerization, sensitivity to stilbene disulfonate-derived inhibitors, and a requirement for an acidic residue at the solute binding site. We also identify several amino acids critical for Bor1p function and show that disease-causing mutations in human SLC4A1 will eliminate in vivo function when their homologous mutations are introduced in Bor1p. Our data help elucidate mechanistic features of Bor1p and reveal significant functional properties shared between borate transporters and SLC4 transporters.

Human SLC4A11 does not complement BOR1 or support borate transport in Saccharomyces cerevisiae.

Borate is an essential micronutrient in plants regulated by borate transporters, which also protect both yeast and plants from toxically high levels of borate and share homology with the human SLC4 transporters. SLC4A11 is linked to congenital hereditary endothelial dystrophy and was initially reported to transport borate before subsequent studies rebutted this conclusion. To better understand the transport activities of purported borate transporters, we tested the ability of SLC4A11 and eleven borate transporters from A. thaliana and O. sativa to complement a BOR1 deletion in S. cerevisiae . We show that AtBOR4 , AtBOR5 , AtBOR7 , OsBOR2 , and OsBOR3 can each complement ScBOR1 , while the rest of the transporters tested do not rescue growth. Additionally, quantification of intracellular borate content demonstrates that SLC4A11 does not export borate in yeast, supporting studies that its transported substrate is not borate.