PT - JOURNAL ARTICLE AU - Elizabeth A. Hambleton AU - Victor A.S. Jones AU - Ira Maegele AU - David K vaskoff AU - Timo Sachsenheimer AU - Annika Guse TI - Enhanced Stability of Non-Canonical NPC2 in the symbiosome supports coral-algal symbiosis AID - 10.1101/399766 DP - 2018 Jan 01 TA - bioRxiv PG - 399766 4099 - http://biorxiv.org/content/early/2018/08/25/399766.short 4100 - http://biorxiv.org/content/early/2018/08/25/399766.full AB - Cnidarians such as reef-building corals depend upon nutrient transfer from intracellular symbionts, but the mechanisms and evolution of this process remain unknown. Homologues of the conserved cholesterol binder Niemann-Pick Type C2 (NPC2) in cnidarians are implicated in the transfer of sterol from symbionts. Here, we show that symbionts transfer bulk sterols to the host, host sterol utilization is plastic, and pharmacological inhibition of sterol trafficking disrupts symbiosis. Having undergone an anthozoan-specific expansion, “non-canonical” NPC2s respond to symbiosis and accumulate over time at the lysosomal-like organelle in which the symbiont resides (“symbiosome”). We demonstrate that both a non- and canonical Aiptasia NPC2 bind symbiont-produced sterols, yet only the non-canonical homologue exhibits increased stability at low pH. We propose that symbiotic cnidarians adapted pre-existing cholesterol-trafficking machinery to function in the highly acidic symbiosome environment, allowing corals to dominate nutrient-poor shallow tropical seas worldwide.