Involvement of TauT/SLC6A6 in Taurine Transport at the Blood–Testis Barrier

Abstract

Taurine transport was investigated at the blood–testis barrier (BTB) formed by Sertoli cells. An integration plot analysis of mice showed the apparent influx permeability clearance of [3H]taurine (27.7 μL/(min·g testis)), which was much higher than that of a non-permeable paracellular marker, suggesting blood-to-testis transport of taurine, which may involve a facilitative taurine transport system at the BTB. A mouse Sertoli cell line, TM4 cells, showed temperature- and concentration-dependent [3H]taurine uptake with a Km of 13.5 μM, suggesting that the influx transport of taurine at the BTB involves a carrier-mediated process. [3H]Taurine uptake by TM4 cells was significantly reduced by the substrates of taurine transporter (TauT/SLC6A6), such as β-alanine, hypotaurine, γ-aminobutyric acid (GABA), and guanidinoacetic acid (GAA), with no significant effect shown by L-alanine, probenecid, and L-leucine. In addition, the concentration-dependent inhibition of [3H]taurine uptake revealed an IC50 of 378 μM for GABA. Protein expression of TauT in the testis, seminiferous tubules, and TM4 cells was confirmed by Western blot analysis and immunohistochemistry by means of anti-TauT antibodies, and knockdown of TauT showed significantly decreased [3H]taurine uptake by TM4 cells. These results suggest the involvement of TauT in the transport of taurine at the BTB.

The role of taurine in male reproduction: Physiology, pathology and toxicology

“…great extent (39). Thus, TauT may play an important role in protecting germ cells from oxidative stress by transporting taurine to seminiferous tubules.…”

“…Apart from regulating the hypothalamus and pituitary hormone release, taurine can also directly act on the testis. Abundant taurine existing in testis not only comes from endogenous synthesis in testis stated above, but also can be transported into testis across blood-testis barrier through its special transporters such as SLC6A6, also named as TauT ( 39 ).On the one hand, taurine can directly promote the secretion of T via acting on the Leydig cells of testis ( 30 ). In addition, an in vitro experiment ( 40 ) shows that taurine in interstitial cells can also increase T synthesis by enhancing autophagy process and inhibiting apoptosis.…”

“…Taurine transporters play an important role in taurine transporting of male reproductive system. Firstly, according to the study of uptake and expression, it is found that TauT participates in the transport of taurine in the blood-testis barrier (BTB) and contributes to the internal transport of taurine in BTB to a great extent ( 39 ). Thus, TauT may play an important role in protecting germ cells from oxidative stress by transporting taurine to seminiferous tubules.…”

Taurine and Creatine Transporters as Potential Drug Targets in Cancer Therapy

“…In 2022, taurine uptake was tested by TM4–mouse Sertoli cells, which formed a blood–testis barrier [ 69 ]. Taurine transport was significantly reduced by β-alanine (95.3% uptake inhibition), hypotaurine (86.7%), GABA (76.7%), and GAA (42.7%).…”

“…Taurine transport was significantly reduced by β-alanine (95.3% uptake inhibition), hypotaurine (86.7%), GABA (76.7%), and GAA (42.7%). No significant biological activity was observed for probenecid [ 69 ]. Figure 5 presents two of the tested compounds.…”