RSM requires carboxylmethylation. (A) Models for RSM. In the absence of Rce1p and Ste24p, CaaX proteolysis of a-factor-CKQQ is mediated by either an ER (1) or a non-ER-localized (2) protease (Rsm1p). If the latter, the dependence of RSM on Ste14p indicates that a trafficking step is required to return proteolysed a-factor to the Ste14p ICMT that resides at the ER. Alternatively, non-proteolysed a-factor could promote mating (3). In this scenario, RSM would be independent of Ste14p. ER, endoplasmic reticulum; PM, plasma membrane. (B) Loss of Ste14p in a CaaX protease-deficient strain prevents RSM. The plasmids used were pWS610 and pWS738, which were separately transformed into yWS164 and yWS829. yWS164-derived strains were additionally transformed with pRS316 to provide a comparable set of auxotrophic markers to that of the yWS829-derived strains