[HTML][HTML] Role of phosphatase of regenerating liver 1 (PRL1) in spermatogenesis

Y Bai, HM Zhou, L Zhang, Y Dong, Q Zeng, W Shou… - Scientific reports, 2016 - nature.com
Y Bai, HM Zhou, L Zhang, Y Dong, Q Zeng, W Shou, ZY Zhang
Scientific reports, 2016nature.com
The PRL phosphatases are oncogenic when overexpressed but their in vivo biological
function is less well understood. Previous gene deletion study revealed a role for PRL2 in
spermatogenesis. We report here the first knockout mice lacking PRL1, the most related
homolog of PRL2. We found that loss of PRL1 does not affect spermatogenesis and
reproductive ability of male mice, likely due to functional compensation by the relatively
higher expression of PRL2 in the testes. However, PRL1−/−/PRL2+/− male mice show …
Abstract
The PRL phosphatases are oncogenic when overexpressed but their in vivo biological function is less well understood. Previous gene deletion study revealed a role for PRL2 in spermatogenesis. We report here the first knockout mice lacking PRL1, the most related homolog of PRL2. We found that loss of PRL1 does not affect spermatogenesis and reproductive ability of male mice, likely due to functional compensation by the relatively higher expression of PRL2 in the testes. However, PRL1−/−/PRL2+/− male mice show testicular atrophy phenotype similar to PRL2−/− mice. More strikingly, deletion of one PRL1 allele in PRL2−/− male mice causes complete infertility. Mechanistically, the total level of PRL1 and PRL2 is negatively correlated with the PTEN protein level in the testis and PRL1+/−/PRL2−/− mice have the highest level of PTEN, leading to attenuated Akt activation and increased germ cell apoptosis, effectively halting spermatozoa production. These results provide the first evidence that in addition to PRL2, PRL1 is also required for spermatogenesis by downregulating PTEN and promoting Akt signaling. The ability of the PRLs to suppress PTEN expression underscores the biochemical basis for their oncogenic potential.
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