Study on the novel degradation pathway from recycling endosomes to lysosomes

近年来，小分子GTP酶Rab12被认为是一种新的膜信号转导途径，可调节内小体循环到溶酶体，从而降解循环分子，但其生理意义尚不清楚。在本研究中，我们发现Rab12促进了PAT4(质子偶联氨基酸转运体4)的结构性降解。由于PAT4参与细胞外培养上清液中氨基酸的摄取，因此在MEF细胞中敲除Rab12可以增加细胞内L氨基酸的浓度，从而激活mTORC 1，抑制自噬。我们的发现表明，Rab12通过在质膜上维持适量的PAT4来抑制细胞的过度生长。

Small GTPase Rab12 has recently been suggested to regulate a new membrane traffic pathway form recycling endosomes to lysosomes to degrade recycling molecules, but its physiological significance remained unknown. In this study, we found that Rab12 promotes constitutive degradation of PAT4 (proton-coupled amino-acid transporter 4). Because PAT4 is involved in the uptake of amino acids from the extracellular medium, knockdown of Rab12 in MEF cells increased the intracellular concentration of L-amino acids, resulting in the activation of mTORC1 and inhibition of autophagy. Our findings suggest that Rab12 suppresses excessive cell growth by maintaining the proper amount of PAT4 at the plasma membrane.