Figure 3.

Hypothetical molecular mechanism of CI and rescue by the Wolbachia CI factors based on the TA model. a. Wolbachia CifA and CifB proteins are secreted into the host testis cells. Under normal conditions, CifA binds tightly to CifB to inhibit its premature action during spermatogenesis and facilitate its delivery to the sperm. b. During spermiogenesis, Wolbachia are shed from the mature sperm while CifA and CifB proteins remain in the sperm. c. Upon fertilization, CifA is rapidly degraded by a protease(s). Free CifB protein is now active (Top) unless the egg is infected by the same (or a compatible) strain of Wolbachia that can supply the embryo with fresh CifA protein (Bottom). d. (Top) In an uninfected egg, free CifB likely localizes to the paternal pronucleus where it can interact with paternal chromatin and modify its target(s). (Bottom) If the egg is infected with a compatible strain of Wolbachia, newly synthesized CifA secreted by the bacteria changes the localization of CifB through direct protein–protein interaction, preventing CifB from accessing its target(s). e. (Top) CifB modification of the target (shown as green star on the target) results in aberrant histone deposition and other downstream defects in the paternal pronucleus. (Bottom) CifB neutralization by CifA results in normal protamine–histone exchange in the paternal pronucleus. f. (Top) Improper condensation of the paternal chromosome leads to chromosome mis-segregation during anaphase with chromatin bridging and shearing of paternal DNA. (Bottom) Properly condensed paternal chromosomes in the “rescued” embryo allows for normal mitotic division.