Disease relevance of Slc16a1

• 3. Ex vivo experiments using DB-1 human melanoma xenografts grown in severe combined immunodeficient mice found that MCT-1 and not NHE-1 was a major determinant of DB-1 tumor cell pHi [1].
• To establish its role in the pathogenesis of breast cancer in humans, we generated stable transfectants of MCF7 breast cancer cells negative for endogenous MCT-1 (MCF7-MCT-1) [2].

High impact information on Slc16a1

• Recently, two monocarboxylate transporters, MCT1 and MCT2, have been cloned [3].
• Expression of monocarboxylate transporter mRNAs in mouse brain: support for a distinct role of lactate as an energy substrate for the neonatal vs. adult brain [3].
• Double-labeling experiments reveal that the expression of MCT1 mRNA in endothelial cells is highest at postnatal day 15 and is not detectable at adult stages [3].
• MCT-1 oncogene contributes to increased in vivo tumorigenicity of MCF7 cells by promotion of angiogenesis and inhibition of apoptosis [2].
• Overexpression of a novel oncogene MCT-1 (multiple copies in a T cell malignancy) causes malignant transformation of murine fibroblasts [2].

Biological context of Slc16a1

• Tissue distribution of basigin and monocarboxylate transporter 1 in the adult male mouse: A study using the wild-type and basigin gene knockout mice [4].
• Decreased expression of MCT1 and -4 on the surfaces of Müller and photoreceptor cells may compromise energy metabolism in the outer retina, leading to abnormal photoreceptor cell function and degeneration [5].
• The monocarboxylate transporter MCT4 mediates lactic acid efflux from most tissues that are dependent on glycolysis for their ATP production [6].
• Cross-linking is markedly reduced by those compounds that protect against irreversible inhibition of lactate transport by DIDS and enhanced by imposition of a pH gradient across the plasma membrane to recruit the substrate binding site of MCT1 to an exofacial conformation [7].
• Recent reports by this laboratory and others have demonstrated an association between 5A11/Basigin, a member of the immunoglobulin gene superfamily, and monocarboxylate transporter-1 (MCT1), a lactose transporter [8].

Anatomical context of Slc16a1

• Bsg was absent but MCT1 was present in Sertoli cells, cauda epididymis, myoepithelial cells and duct of the mandibular gland, surface epithelium of the stomach and bronchioles [4].
• In Bsg-KO mice, with the exception of Leydig cells, MCT1 immunostaining was greatly reduced in intensity and its distribution was altered in tissues that expressed both Bsg and MCT1 in WT mice [4].
• Transcripts encoding for MCT1 and MCT2 were present, under a polyadenylated form, in the majority of the human and mouse oocytes and early embryos [9].
• Recently, it was reported that targeting of MCT1 and -4 to the plasma membrane requires association with 5A11/basigin (CD147) [5].
• Under basal conditions, both MCT immunoreactivities (IR) were found in the cell soma and dendrites, although IR for MCT1 appeared less bright than for MCT2 [10].

Associations of Slc16a1 with chemical compounds

• Without glucose, MCT1 mRNA was not expressed, and immunoreactivity dramatically reduced in intensity as morulae died [11].
• Interaction of the erythrocyte lactate transporter (monocarboxylate transporter 1) with an integral 70-kDa membrane glycoprotein of the immunoglobulin superfamily [7].
• Using N-glycanase-F treatment and an in vitro translation system, we provide evidence that this glycosylation site is not actually utilised in Chinese hamster MCT1 [12].
• The mucosal MCT1 was localized in the basolateral membrane of enterocytes, while slc5a8 was restricted to the apical cell membrane, suggesting the involvement of slc5a8 in the uptake of luminal SCFA, and of MCT1 in the efflux of SCFA and monocarboxylate metabolites towards blood circulation [13].
• Tissue-specific thyroid hormone deprivation and excess in monocarboxylate transporter (mct) 8-deficient mice [14].

Co-localisations of Slc16a1

• Immunohistochemistry demonstrated that Bsg colocalized with MCT1 in the cerebrum, retina, skeletal and cardiac muscle, duodenal epithelium, hepatic sinusoid, proximal uriniferous tubules, Leydig cells, and efferent ductule epithelium in WT mice [4].

Other interactions of Slc16a1

• On the other hand, immunostaining patterns in cells in which Bsg was absent but MCT1 was present in WT mice remained unchanged in Bsg-KO mice [4].
• These studies have shown that mild exercise training fails to increase MCT4 and that changes in MCT1 are complex, depending not only the accumulated exercise but also on the stage of training [15].
• For embryos derived in vivo and those cultured with glucose, MCT1 mRNA was present throughout preimplantation development, protein immunoreactivity appearing diffuse throughout the cytoplasm with brightest intensity in the outer cortical region of blastomeres [11].
• In contrast, several elements expressing the S100beta protein, another astrocytic marker found to be located in distinct parts of the same cell when compared with glial fibrillary acidic protein, were also strongly immunoreactive for MCT1, suggesting expression of this transporter by astrocytes [16].
• The 70-kDa protein that is cross-linked to MCT1 was purified and shown to contain N-linked carbohydrate; the apparent core molecular mass is 40 kDa [7].

Analytical, diagnostic and therapeutic context of Slc16a1

• RT-PCR analyses of mRNA levels from wild-type and Bsg(-/-) mice demonstrated that the MCT1 transcript was expressed at normal levels in Bsg(-/-) mice [5].
• To clarify the role of MCT in development, transport characteristics for DL-lactate were examined, as were mRNA expression and protein localisation for MCT1 and MCT3, using confocal laser scanning immunofluorescence in freshly collected and cultured embryos [11].
• We report here the characterization by Northern blot analysis and by in situ hybridization of the expression of MCT1 and MCT2 mRNAs in the mouse brain [3].
• Although previous Northern blot and in situ hybridization studies suggested that neurons express the monocarboxylate transporter MCT2, subsequent immunohistochemical analyzes either failed to confirm the presence of this transporter or revealed only a low density of immunolabeled neuronal processes in vivo [17].
• Cell-specific localization of monocarboxylate transporters, MCT1 and MCT2, in the adult mouse brain revealed by double immunohistochemical labeling and confocal microscopy [16].

References