AE3 anion exchanger isoforms in the vertebrate retina: developmental regulation and differential expression in neurons and glia

Abstract

Plasma membrane anion exchangers constitute a multigene family that contributes to the regulation of intracellular pH and chloride concentration in many cell types. We have characterized two polypeptide isoforms of the AE3 gene that are expressed in the rat retina. Using antipeptide antibodies specific for defined NH2-terminal and COOH- terminal epitopes, we have identified a 165 kDa polypeptide whose expression is restricted to the primary glial cell type of the retina, the Muller cell, and a 125 kDa polypeptide that is expressed in horizontal neurons. Expression of the Muller cell isoform exhibits a polarized distribution and is highest in basal endfoot processes. These AE3 isoforms exhibit a distinct developmental expression pattern in postnatal rat retina. The neuronal isoform is undetectable in neonatal retina until postnatal day 10–15, correlating strongly with the onset of retinal function.

Non–cell-autonomous factor induces the transition from excitatory to inhibitory GABA signaling in retina independent of activity

“…Possible mechanisms include regulation of a large number of proteins, including cation-chloride cotransporters (12), namely the Na + -K + -2Cl − cotransporters that increase [Cl − ] i (10,(31)(32)(33)(34)(35) (42), and a variety of chloride channels (13). In contrast to the hippocampus, RGCs do not express Na + -K + -2Cl − cotransporter 1 (23) and they do not express Cl − /HCO 3 + exchangers until later in development (43). Hence the source of their high [Cl − ] i levels during early development is not known.…”

Molecular physiology and genetics of Na+-independent SLC4 anion exchangers

“…Two independently derived Ae3 -/-mice have exhibited no cardiac phenotype, but cardiac contractility in vivo, in perfused heart, and in isolated cardiomyocytes was impaired in the combined genetic absence of the two chloride loaders Ae3 and Nkcc1 (Prasad et al, 2008). Distinct Ae3 isoforms are also expressed in Muller cells and horizontal neurons of the retina (Kobayashi et al, 1994). One line of Ae3 -/-mice exhibits late onset retinal degeneration and progressive blindness at 4-6 months of age, accompanied by upregulation of NBCe1/SLC4A4, CAII and CAIV (Alvarez et al, 2007a).…”

Bicarbonate homeostasis in excitable tissues: role of AE3 Cl−/HCO3− exchanger and carbonic anhydrase XIV interaction

“…The mammalian inner retina expresses AE3fl in Müller cells and AE3c horizontal neurons (14). Double-labeling immunostaining of frozen vertical retina sections from adult mice, combined with confocal immunofluorescence microscopy, was used to reexamine the expression of the two alternate AE3 proteins.…”

“…The COOH-terminal 957 amino acids of both polypeptides are identical, but AE3c contains a unique NH 2 (5). Excitable (neuron) and support (glial) brain cells express only the ϳ160 kDa AE3fl isoform (15), while inner retina, which is also part of the central nervous system (CNS), expresses both AE3fl and AE3c isoforms, in neuronal and glial cells (14).…”