SAS6

SAS6 (PF3D7_0607600) is a basal body component required for the de novo assembly and duplication of basal bodies during male gametogenesis in Plasmodium (PMID:25154861, PMID:35077503). In P. berghei, genetic knockout of SAS6 severely disrupts male gametogenesis, producing reduced basal body numbers, axonemal assembly defects, and abnormal nuclear allocation, and it blocks transmission from mosquito to vertebrate host at the ookinete-to-sporulating oocyst transition (PMID:25154861). Structurally, the eight basal bodies are concomitantly assembled de novo from a deuterosome-like structure in a manner dependent on both SAS6 and SAS4; within each basal body, SAS6 and centrin occupy distinct subdomains of the fused proximal/central core lumen, surrounded by a SAS4-toroid inside the microtubule wall (PMID:35077503). Beyond this basal body assembly role established in P. berghei, no further mechanistic detail for SAS6 has been characterized in the available corpus.

1. 2014 High

   It was unknown what drives basal body formation and male gamete maturation in Plasmodium; knocking out SAS6 established that it is required for basal body assembly and duplication and for onward transmission to the mosquito vector.

   Evidence Genetic knockout with electron microscopy and transmission assays in P. berghei

   PMID:25154861

   Open questions at the time

   • Does not resolve the molecular activity of SAS6 (e.g. self-oligomerization or partner binding) underlying basal body assembly
   • Mechanism linking basal body loss to abnormal nuclear allocation not defined
   • No P. falciparum data despite the subject gene identifier being PF3D7_0607600
2. 2022 High

   The spatial architecture and assembly route of the basal body were unknown; expansion microscopy placed SAS6 in a distinct core subdomain and showed the eight basal bodies arise concomitantly de novo from a deuterosome-like structure in a SAS6/SAS4-dependent manner.

   Evidence Ultrastructure expansion microscopy (U-ExM), Pan-ExM, bulk proteome labelling, and 3D reconstruction in P. berghei

   PMID:35077503

   Open questions at the time

   • The direct molecular interaction between SAS6, SAS4, and centrin within the core is not biochemically defined
   • How SAS6 is recruited to or nucleates the deuterosome-like structure is unresolved
   • Single-lab structural characterization

• The biochemical activity of SAS6 and its direct binding partners within the basal body core remain undefined, as does whether its role is conserved in P. falciparum.
• No reconstitution or direct interaction assay establishing SAS6 molecular activity
• No characterization in P. falciparum (PF3D7_0607600) itself
• Structural relationship of SAS6 to centrin and SAS4 shown by localization but not by direct binding data