A phosphoinositide-mediated switch of GET pathway receptor dimerization in <i>Arabidopsis</i>

The Guided Entry of Tail-Anchored Proteins (GET) pathway facilitates the insertion of tail-anchored (TA) proteins into the ER membrane, but its regulation in plants remains unclear. In <i>Arabidopsis</i>, we identify phosphatidylinositol 4-phosphate (PI4P) as an anchor that brings the receptors <i>At</i>GET1 and <i>At</i>GET2 into proximity within the ER membrane. <i>At</i>GET2 binds PI4P via an arginine residue in its transmembrane domain. Mutation of this residue disrupts <i>At</i>GET1 and <i>At</i>GET2 proximity at the ER, impairing GET complex function. This defect can be rescued by synthetic dimerization of <i>A</i>tGET1 and <i>At</i>GET2. The PI4P phosphatase RHD4 acts as a gatekeeper, converting PI4P to PI and enabling <i>At</i>GET1-<i>At</i>GET2 interaction, which influences TA protein insertion and root hair growth. Our findings establish the PI4P-RHD4 module as a crucial regulator of GET receptor dynamics, highlighting the interplay between phospholipids and protein trafficking in plants.