Carboxyl-methylation of prenylated calmodulin CaM53 is required for efficient plasma membrane targeting of the protein

Prenylation is necessary for association of the petunia calmodulin CaM53 wi th the plasma membrane. To determine whether post-prenylation processing of the protein was also required for plasma membrane targeting, we studied th e subcellular Idealization of a GFP-labelled CaM53 reporter in yeast and pl ant cells. Blocking of carboxyl-methylation of prenylated proteins either b y a specific inhibitor or in mutant yeast cells resulted in localization of green fluorescence to what appears to be the endomembrane system, in contr ast with the plasma membrane localization observed in control cells. We sho w that a prenyl-cysteine methyltransferase (PCM) activity that carboxyl-met hylates prenylated CaM53 also exists in plant cells, and that it is require d for efficient plasma membrane targeting. We also report an Arabidopsis ge ne with homology to PCM and demonstrate that it encodes a protein with PCM activity that localizes to the endomembrane system of plant cells, similar to prenylated but unmethylated CaM53. Together, our data suggest that, foll owing prenylation, CaM53 is probably associated with the endomembrane syste m, where a PCM activity methylates the prenylated protein prior to targetin g it to its final destination in the plasma membrane.