Fig. 7.

A proposed regulatory network between K⁺ transporters and cyclic diadenylate monophosphate (c-di-AMP) metabolic enzymes. Solid brown curved lines with arrowhead indicate enzymatic reactions, while dashed brown curved lines indicate indirect activation. Solid red lines without arrowhead indicate inhibition. Also, solid brown straight lines indicate K⁺ uptake and solid red straight lines indicate K⁺ efflux. c-di-AMP (red dumbbell) is synthesized by DisA, CdaA, or CdaS from two molecules of ATP (blue dot) and hydrolyzed by GdpP, PgpH, or YtpI to pApA (pink dumbbell) or AMP (pink dot). Factors spatially and temporally controlled the level of c-di-AMP by these enzymes may affect the cognate protein expression in transcription, translation, and so on. For examples, CdaR represses CdaA activity, GlmM represses CdaA, RadA inhibits DisA, (p)ppGpp (blue oval) inhibits GdpP and PgpH, K⁺ (green dot) down-regulates the protein level of CdaA. KimA (green complex), Trk (blue complex), Ktr (pink complex), and Kdp system (orange complex) are responsible for the K⁺ transport. KefA (purple complex) is responsible for K⁺ efflux. c-di-AMP binds to c-di-AMP riboswitch (black lines with clover structure) to promote transcriptional termination, thus down-regulating kdp operon and kimA expression