Monocarboxylate transporter MCT1 is located in the apical membrane and MCT3 in the basal membrane of rat RPE

Abstract

The retinal pigment epithelium (RPE) forms the outer blood-retinal barrier and regulates the movement of nutrients, water, and ions between the choroidal blood supply and the retina. The transport properties of the RPE maintain retinal adhesion and regulate the pH and osmolarity in the space surrounding the photoreceptor cell outer segments. In this report we identify two monocarboxylate transporters, MCT1 and MCT3, expressed in rat RPE. On the basis of Northern and Western blot analyses, MCT1 is expressed in both the neural retina and the RPE, whereas the expression of MCT3 is restricted to the RPE. Using indirect immunolocalization we show that the two transporters are polarized to distinct membrane domains. MCT1 antibody labels the apical surface and the apical processes of the RPE. A polyclonal antibody produced against the carboxy terminus of rat MCT3 labels only the basolateral membrane of the RPE. The demonstration of MCT1 on the apical membrane and MCT3 on the basal membrane identifies specific proteins involved in the discriminate and critical regulation of water and lactate transport from the retina to the choroid.

Mechanisms regulating tissue-specific polarity of monocarboxylate transporters and their chaperone CD147 in kidney and retinal epithelia

“…Our observations in MDCK cells indicate that MCT1 does not possess sorting signals, and CD147 is the dominant sorting partner that determines the basolateral localization of the MCT1-CD147 lactate transport complex. In RPE, endogenous CD147 and MCT1 are both expressed predominantly in the apical membrane (25,28). As previous data from our laboratory demonstrate that the basolateral signal of CD147 is not recognized by RPE, resulting in its predominant apical localization (32), the MDCK experiments reported here strongly support a scenario in which the apical localization of MCT1 is determined by apically targeted CD147.…”

“…4). Our observation is similar to what has been described in RPE in situ (6,10,14,25,26). Furthermore, the human RPE cell line ARPE-19 expresses CD147 and MCT1 at the apical membrane and MCT4 and CD147 at the basolateral membrane (ref.…”

“…Knockout mice for the MCT chaperone CD147 exhibit physiological and morphological alterations of the retina (23,24). Retinal lactate levels are regulated by the retinal pigment epithelium (the blood-retinal barrier for the outer retina) via apically localized MCT1 (6,10,25) and basolaterally localized MCT3 (25,26). A third member of the MCT family, MCT4, is normally not expressed in adult retinal pigment epithelium (RPE) but is expressed basolaterally in the human RPE cell line ARPE-19 (27).…”

Carbonic anhydrase XIV is enriched in specific membrane domains of retinal pigment epithelium, Müller cells, and astrocytes

“…Like CA XIV, MCT1 is strongly enriched in the microvilli of the RPE and is also found in the microvilli of Müller cells (28). MCT1 is not significantly expressed in glial endfeet and basolateral membrane domains of RPE, but these membrane domains appear to contain MCT4 (unpublished observation) and MCT3, respectively (29).…”

Lactate Transport and Signaling in the Brain: Potential Therapeutic Targets and Roles in Body—Brain Interaction

“…52,53 MCT3 has an intermediate affinity (Km 6 mmol/L) 54 and is predominantly expressed in retinal epithelial cells and in the choroid plexus epithelial cells (which are developmentally homologous to the latter), but not in the ependymal cells lining the cerebral ventricles. 17 The high-affinity transporter MCT2 is abundantly detected on neurons and astrocytes by immunohistochemical methods, 55 but shows substantial species differences in distribution. In rat brain, MCT2 immunoreactivity has primarily been found on perivascular endfeet 8,9,56 and postsynaptic densities.…”