RT Journal Article
SR Electronic
T1 Rod-shaped tricalbins contribute to PM asymmetry at curved ER-PM contact sites
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 579128
DO 10.1101/579128
A1 Hoffmann, Patrick C.
A1 Bharat, Tanmay A. M.
A1 Wozny, Michael R.
A1 Miller, Elizabeth A.
A1 Kukulski, Wanda
YR 2019
UL http://biorxiv.org/content/early/2019/03/15/579128.abstract
AB Lipid flow between cellular organelles occurs via membrane contact sites that form dynamic conduits. Extended-synaptotagmins, known as tricalbins in yeast, mediate lipid transfer between the endoplasmic reticulum (ER) and plasma membrane (PM). How these proteins regulate the membrane architecture to transport lipids across the aqueous space between bilayers remains unknown. Using correlative microscopy, electron cryo-tomography and high-throughput genetics we address this interplay of architecture and function in budding yeast. We find that ER-PM contacts are diverse in protein composition and membrane morphology, not in intermembrane distance. In situ cryo-EM of tricalbins reveals their molecular organisation that suggests an unexpected structural framework for lipid transfer. Genetic analysis identifies functional redundancies, both for tricalbin domains and cellular lipid routes, and points to tricalbin function in maintenance of PM asymmetry. These results uncover a modularity of molecular and structural functions of tricalbins, and of their roles within the network of cellular lipid fluxes.