Slm1, an F‐ BAR and PH domain‐containing protein, regulates heat‐induced turnover of nutrient transporter to control plasma‐membrane quality

Cells must rapidly reorganize plasma membrane (PM) architecture to withstand heat stress, yet how PM quality control (PMQC) is coordinated with stress-activated signaling pathways remains poorly understood. In budding yeast, heat stress activates both the cell wall integrity (CWI) pathway and PMQC: the former repairs cell wall damage through the Rho1-Pkc1-MAPK cascade, whereas the latter removes heat-damaged amino acid-polyamine-organocation (APC) transporters via ubiquitin-dependent endocytosis. Eisosomes are PM invaginations that harbor multiple APC transporters together with the F-BAR- and PH-domain-containing proteins Slm1/Slm2, which upon stress relocalize to TORC2-containing domains to promote sphingolipid synthesis. Although Slm proteins participate in stress adaptation, how the abundance of Slm proteins affects PMQC is unknown. To address this question, we engineered a Tet-off strain that enables controlled expression of GFP-tagged Slm1 (GFP-Slm1) and found that Slm1 is massively overexpressed (~ 48-fold) in the absence of doxycycline. GFP-Slm1 overexpression caused strong temperature and canavanine sensitivity and produced abnormal cortical actin organization together with defective recycling of PM proteins, including the v-SNARE Snc1. Notably, these actin and trafficking defects were further exacerbated in eisosome-deficient cells, where excess GFP-Slm1 redistributed broadly along the PM and formed prominent membrane-associated aggregates. Under heat stress, excess Slm1 selectively delays the endocytic turnover and vacuolar degradation of heat-damaged APC transporters, leading to their prolonged accumulation at the PM. Together, our findings identify Slm1 as a regulator of PMQC that modulates the heat-induced turnover of nutrient transporters and other PM proteins and reveal that eisosome function buffers against Slm1-driven defects in actin-dependent membrane trafficking.