Elevated NAD⁺ drives Sir2A-mediated GCβ deacetylation and OES localization for Plasmodium ookinete gliding and mosquito infection.

ABSTRACT: cGMP signal-activated ookinete gliding is essential for mosquito midgut infection of Plasmodium in malaria transmission. During ookinete development, cGMP synthesizer GCβ polarizes to a unique localization "ookinete extrados site" (OES) until ookinete maturation and activates cGMP signaling for initiating parasite motility. However, the mechanism underlying GCβ translocation from cytosol to OES remains elusive. Here, we use protein proximity labeling to search the GCβ-interacting proteins in ookinetes of the rodent malaria parasite P. yoelii, and find the top hit Sir2A, a NAD⁺-dependent sirtuin family deacetylase. Sir2A interacts with GCβ throughout ookinete development. In mature ookinetes, Sir2A co-localizes with GCβ at OES in a mutually dependent manner. Parasites lacking Sir

SUBMITTER: Shi Y 

PROVIDER: S-EPMC11885453 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature