Figure 9. Model for Protrudin- and FYCO1-mediated mTOR activation. (A) Under nutrient starvation conditions, lysosomes localize perinuclearly, mTORC1 is predominantly cytosolic, and VPS34 activity on LyLEs is low. The lack of PtdIns3P prevents Protrudin-mediated ER–endosome contacts. (B) The presence of amino acids stimulates the recruitment of the mTORC1 complex to lysosomes. In addition, amino acids activate VPS34 to produce PtdIns3P at the lysosomal membrane. The PtdIns3P-binding protein FYCO1 is recruited to lysosomes, and Protrudin can mediate PtdIns3P-dependent ER–lysosome contact. In such contact sites, the microtubule motor Kinesin-1 is transferred from Protrudin to FYCO1. (C) Lysosomes loaded with Kinesin-1 are translocated along microtubules to the cell periphery. This brings the lysosomal mTORC1 complex in close apposition to nutrient signaling complexes at the plasma membrane and increases mTORC1 activity.
Figure 9.

Model for Protrudin- and FYCO1-mediated mTOR activation. (A) Under nutrient starvation conditions, lysosomes localize perinuclearly, mTORC1 is predominantly cytosolic, and VPS34 activity on LyLEs is low. The lack of PtdIns3P prevents Protrudin-mediated ER–endosome contacts. (B) The presence of amino acids stimulates the recruitment of the mTORC1 complex to lysosomes. In addition, amino acids activate VPS34 to produce PtdIns3P at the lysosomal membrane. The PtdIns3P-binding protein FYCO1 is recruited to lysosomes, and Protrudin can mediate PtdIns3P-dependent ER–lysosome contact. In such contact sites, the microtubule motor Kinesin-1 is transferred from Protrudin to FYCO1. (C) Lysosomes loaded with Kinesin-1 are translocated along microtubules to the cell periphery. This brings the lysosomal mTORC1 complex in close apposition to nutrient signaling complexes at the plasma membrane and increases mTORC1 activity.

This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal