FLCN is a novel Rab11A-interacting protein and is involved in the Rab11A-mediated recycling transport

Abstract

The Birt-Hogg-Dubé (BHD) syndrome related protein FLCN has recently been implicated in the vesicular trafficking processes by interacting with several Rab family GTPases. In the previous studies, we have shown that FLCN could inhibit the binding of overexpressed PAT1, which is a membrane-bound amino acid transporter, to the lysosome in human embryonic kidney 293 cells. This tends to stabilize the lysosomal amino acid pool that is a critical signal to activate the mTORC1 signalling pathway. However, the mechanisms of FLCN during this process remain unexplored. Here we report that FLCN can bind via its C-terminal DENN-like domain to the recycling transport regulator, Rab11A. Suppression of either Rab11A or FLCN facilitated the localization of the overexpressed PAT1 on the lysosome and inhibited its targeting on the plasma membrane. As a consequence, the mTORC1 was down-regulated. The in vitro GEF activity assay does not support FLCN modifies the Rab11A activity directly. Instead, we found FLCN promoted the loading of PAT1 on Rab11A. Our data uncover a function of FLCN in the Rab11A-mediated recycling pathway and may provide new clues to understand the BHD conditions.