MCT1 and its accessory protein CD147 are differentially regulated by TSH in rat thyroid cells

Fanelli, Albertina; Grollman, Evelyn F.; Wang, Dian; Philp, Nancy J.

doi:10.1152/ajpendo.00172.2003

Cited by 43 publications

(42 citation statements)

References 28 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overexpression of MCT4 did not affect cellular levels of MCT1, suggesting that CD147 is constitutively expressed. Consistent with previous work from our laboratory (33), these studies show that it is expression of MCTs that regulates the abundance of the mature transporter complex. This interpretation is further supported by our findings showing that stable expression of CD147 in HEK293 cells did not increase the level of MCT1.…”

Section: Discussionsupporting

confidence: 91%

Monocarboxylate Transporter 4 Regulates Maturation and Trafficking of CD147 to the Plasma Membrane in the Metastatic Breast Cancer Cell Line MDA-MB-231

Gallagher¹,

Castorino

Wang³

et al. 2007

Cancer Research

Self Cite

254

237

View full text Add to dashboard Cite

Metastatic cancer cells increase glucose consumption and metabolism via glycolysis, producing large quantities of lactate. Recent work has shown that lactate efflux is mediated by monocarboxylate transporters (MCT), which are composed of a catalytic unit (MCT) and an accessory subunit (CD147), comprising the functional lactate transporter. CD147, an extracellular matrix metalloproteinase (MMP) inducer, is highly expressed in metastatic cancer cells. Because aerobic glycolysis is a hallmark of metastatic cancer, we examined whether increases in CD147 expression were linked to MCT expression in MDA-MB-231, a highly metastatic breast cancer cell line. MCT4 mRNA and protein expression were increased in MDA-MB-231 cells compared with cells derived from normal mammary tissue. MCT4 colocalized with CD147 in the plasma membrane and in membrane blebs shed from the cell surface. Small interfering RNA-mediated silencing of MCT4 impaired the maturation and trafficking of CD147 to the cell surface, resulting in accumulation of CD147 in the endoplasmic reticulum. Silencing MCT4 also resulted in fewer membrane blebs and decreased migration of MDA-MB-231 cells in vitro. Knockdown of CD147 resulted in loss of MCT4 in the plasma membrane and accumulation of the transporter in endolysosomes. These studies establish for the first time that increased expression of CD147 in metastatic cancer cells is coupled to the up-regulation of MCT4. The synergistic activities of the MCT/CD147 complex could facilitate migration of tumor cells by CD147-mediated MMP induction and lactate-stimulated angiogenesis and hyaluronan production. These data provide a molecular link between two hallmarks of metastatic cancer: the glycolytic switch and increased expression of CD147. [Cancer Res 2007;67(9):4182-9]

show abstract

Section: Discussionsupporting

confidence: 91%

Monocarboxylate Transporter 4 Regulates Maturation and Trafficking of CD147 to the Plasma Membrane in the Metastatic Breast Cancer Cell Line MDA-MB-231

Gallagher¹,

Castorino

Wang³

et al. 2007

Cancer Research

Self Cite

254

237

View full text Add to dashboard Cite

show abstract

“…Several proteins show cell-specific variations in trafficking. [108][109][110][111][112] To demonstrate the remarkable capacity of the protein trafficking system to adapt to the physiologic requirements of particular cell states and tissues, we will focus on cell types in which the Na,K-ATPase complex exhibits an apical localization. As previously mentioned, the Na,K-ATPase complex localizes to the basolateral membrane of most polarized cells, where it plays an important role in the regulation of ion transport.…”

Section: Cell-specific Variations In Traffickingmentioning

confidence: 99%

Trafficking to the Apical and Basolateral Membranes in Polarized Epithelial Cells

Stoops

Caplan

2014

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Renal epithelial cells must maintain distinct protein compositions in their apical and basolateral membranes in order to perform their transport functions. The creation of these polarized protein distributions depends on sorting signals that designate the trafficking route and site of ultimate functional residence for each protein. Segregation of newly synthesized apical and basolateral proteins into distinct carrier vesicles can occur at the trans-Golgi network, recycling endosomes, or a growing assortment of stations along the cellular trafficking pathway. The nature of the specific sorting signal and the mechanism through which it is interpreted can influence the route a protein takes through the cell. Cell type-specific variations in the targeting motifs of a protein, as are evident for Na,K-ATPase, demonstrate a remarkable capacity to adapt sorting pathways to different developmental states or physiologic requirements. This review summarizes our current understanding of apical and basolateral trafficking routes in polarized epithelial cells.

show abstract

“…Ϫ/Ϫ mouse retinas using a lactic acid dehydrogenase based kit (Trinity Biotech, St. Louis, MO) as previously described (13). Briefly, dark-adapted mice were euthanized in the light by lethal injection and the eyes enucleated.…”

Section: Mct3mentioning

confidence: 99%

Altered visual function in monocarboxylate transporter 3 (Slc16a8) knockout mice

Daniele¹,

Sauer²,

Gallagher³

et al. 2008

American Journal of Physiology-Cell Physiology

Self Cite

View full text Add to dashboard Cite

To meet the high-energy demands of photoreceptor cells, the outer retina metabolizes glucose through glycolytic and oxidative pathways, resulting in large-scale production of lactate and CO2. Mct3, a protoncoupled monocarboxylate transporter, is critically positioned to facilitate transport of lactate and H ϩ out of the retina and could therefore play a role in pH and ion homeostasis of the outer retina. Mct3 is preferentially expressed in the basolateral membrane of the retinal pigment epithelium and forms a heteromeric complex with the accessory protein CD147. To examine the physiological role of Mct3 in the retina, we generated mice with a targeted deletion in Mct3 (slc16A8). The overall retinal histology of 4-to 36-wk-old Mct3Ϫ/Ϫ mice appeared normal. In the absence of Mct3, expression of CD147 was lost from the basolateral but not apical RPE. The saturated a-wave amplitude (amax) of the scotopic electroretinogram (ERG) was reduced by approximately twofold in Mct3 Ϫ/Ϫ mice relative to wildtype mice. A fourfold increase in lactate in the retina suggested a decrease in outer-retinal pH. In single-cell recordings from superfused retinal slices, saturating amplitudes of single rod photocurrents (Jmax) were comparable indicating that Mct3 Ϫ/Ϫ mouse photoreceptor cells were inherently healthy. Based on these data, we hypothesize that disruption of Mct3 leads to a potentially reversible decrease in subretinal space pH, thereby reducing the magnitude of the light suppressible photoreceptor current. monocarboxylate transporter 3; lactate transport; retinal pigment epithleium; pH regulation; photoreceptor; electroretinogram THE RETINAL PIGMENT EPITHELIUM (RPE) forms the outer-blood retinal barrier and performs many functions essential for maintaining the health and functional activity of photoreceptors. Interposed between the choroidal vessels and the photoreceptor cells, the RPE regulates the transport of glucose to the avascular outer retina. Eighty percent of the glucose transported into the outer retina is metabolized via glycolysis producing large amounts of lactate both in the light and the dark (41,42,44). Lactate produced by glycolysis in Müller glia is then used to fuel oxidative phosphorylation in photoreceptor cells (35). The transfer of lactate from glia to neurons is facilitated by proton-coupled monocarboxylate transporters and has been referred to as the "lactate shuttle" (27). Inhibition of monocarboxylate transport or glycolysis results in attenuation of light-

show abstract

MCT1 and its accessory protein CD147 are differentially regulated by TSH in rat thyroid cells

Cited by 43 publications

References 28 publications

Monocarboxylate Transporter 4 Regulates Maturation and Trafficking of CD147 to the Plasma Membrane in the Metastatic Breast Cancer Cell Line MDA-MB-231

Monocarboxylate Transporter 4 Regulates Maturation and Trafficking of CD147 to the Plasma Membrane in the Metastatic Breast Cancer Cell Line MDA-MB-231

Trafficking to the Apical and Basolateral Membranes in Polarized Epithelial Cells

Altered visual function in monocarboxylate transporter 3 (Slc16a8) knockout mice

Contact Info

Product

Resources

About