PT - JOURNAL ARTICLE AU - Ffion B Thomas AU - Deike J Omnus AU - Jakob M Bader AU - Gary HC Chung AU - Nozomu Kono AU - Christopher J Stefan TI - Tricalbin proteins regulate plasma membrane phospholipid homeostasis AID - 10.26508/lsa.202201430 DP - 2022 Aug 01 TA - Life Science Alliance PG - e202201430 VI - 5 IP - 8 4099 - https://www.life-science-alliance.org/content/5/8/e202201430.short 4100 - https://www.life-science-alliance.org/content/5/8/e202201430.full SO - Life Sci. Alliance2022 Aug 01; 5 AB - The evolutionarily conserved extended synaptotagmin (E-Syt) proteins are calcium-activated lipid transfer proteins that function at contacts between the ER and plasma membrane (ER-PM contacts). However, roles of the E-Syt family members in PM lipid organisation remain incomplete. Among the E-Syt family, the yeast tricalbin (Tcb) proteins are essential for PM integrity upon heat stress, but it is not known how they contribute to PM maintenance. Using quantitative lipidomics and microscopy, we find that the Tcb proteins regulate phosphatidylserine homeostasis at the PM. Moreover, upon heat-induced membrane stress, Tcb3 co-localises with the PM protein Sfk1 that is implicated in PM phospholipid asymmetry and integrity. The Tcb proteins also control the PM targeting of the known phosphatidylserine effector Pkc1 upon heat-induced stress. Phosphatidylserine has evolutionarily conserved roles in PM organisation, integrity, and repair. We propose that phospholipid regulation is an ancient essential function of E-Syt family members required for PM integrity.