PT  - JOURNAL ARTICLE
AU  - Patrick C. Hoffmann
AU  - Tanmay A. M. Bharat
AU  - Michael R. Wozny
AU  - Elizabeth A. Miller
AU  - Wanda Kukulski
TI  - Rod-shaped tricalbins contribute to PM asymmetry at curved ER-PM contact sites
AID  - 10.1101/579128
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 579128
4099  - http://biorxiv.org/content/early/2019/03/15/579128.short
4100  - http://biorxiv.org/content/early/2019/03/15/579128.full
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.