Cloning and identification of two novel NBCe1 splice variants from mouse reproductive tract tissues: A comparative study of NCBT genes

Abstract

Na(+)-coupled HCO(3)(-) transporters (NCBTs) of the SLC4 family play critical roles in pH regulation as well as transepithelial HCO(3)(-) transport. We systematically examined, in the mouse reproductive tract tissues, the mRNA expression of five NCBTs as well as the five NBCe1 (Slc4a4) variants NBCe1-A through -E, of which NBCe1-D and NBCe1-E are novel. Cloning of NBCe1-D and NBCe1-E, both lacking a 27-nucleotide cassette I, reveals a novel alternative splicing unit in the mouse Slc4a4 gene. Transcripts of Slc4a4 lacking cassette I are expressed in diverse murine tissues as shown by RT-PCR analysis and in diverse tissues of other vertebrate species as shown by blast against GenBank database. Genomic sequence analysis indicates that cassette I of SLC4A4 is conserved in all NCBT genes except for SLC4A5, which presumably lost cassette I during its evolution. Our present study represents an important step towards understanding the molecular physiology of NBCe1, and presumably other NCBTs.

The Divergence, Actions, Roles, and Relatives of Sodium-Coupled Bicarbonate Transporters

“…The effect of losing cassette I is unknown, although cassette I does contain a consensus casein kinase II phosphorylation site (599), indicating a regulatory role. Transcripts lacking cassette I appear to be widely distributed but only account for a small fraction of the pool of total NBCe1 transcripts that had previously been identified as NBCe1-A/B in any given organ (599). Omission of cassette I from NBCe1-C-like transcripts has not been reported.…”

Interplay between Disulfide Bonding and N-Glycosylation Defines SLC4 Na+-coupled Transporter Extracellular Topography

“…The human SLC4A4 gene encodes three NBCe1 protein variants (-A, -B, and -C), and additional transcripts (-D and -E) have been reported in mouse (7)(8)(9). These variants differ in their Nand C-terminal regions but have the identical transmembrane region (8).…”

Relief of autoinhibition of the electrogenic Na-HCO3cotransporter NBCe1-B: role of IRBIT vs. amino-terminal truncation

“…Mammalian orthologs of NBCe1-A were subsequently cloned from human and rat kidney cDNA libraries (5,21). We now know that there are at least five mammalian NBCe1 gene products, NBCe1-A through NBCe1-E (4,14). NBCe1-A is predominantly expressed in the kidney, NBCe1-B is widely expressed throughout the body, and NBCe1-C is thought to be mainly expressed in the brain.…”