Small proteins modulate ion channel-like ACD6 to regulate immunity inArabidopsis thaliana

SUMMARY ACCELERATED CELL DEATH 6 (ACD6) mediates a trade-off between growth and defense in Arabidopsis thaliana . However, the precise biochemical mechanism by which ACD6 and related proteins in plants act remains enigmatic. Here, we identified two loci, MODULATOR OF HYPERACTIVE ACD6 1 ( MHA1 ) and its paralog MHA1-LIKE ( MHA1L ), that code for ∼7 kDa proteins that differentially interact with specific ACD6 variants. MHA1L enhances accumulation of an ACD6 complex, thereby increasing activity of the ACD6 standard allele for regulating plant growth and defenses. ACD6 is a multipass transmembrane protein with intracellular ankyrin repeats that are structurally similar to those found in mammalian ion channels. Several lines of evidence link increased ACD6 activity to enhanced calcium influx, likely mediated by ACD6 itself and with MHA1L as a direct regulator of ACD6.