Slm1, an F-BAR and PH domain-containing protein, regulates heat-induced turnover of nutrient transporter to control...

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.