A region containing a proline-rich motif targets sG(i2) to the Golgi apparatus

The central function of heterotrimeric GTP-binding proteins (G proteins) is the transduction of extracellular signals, via membrane receptors, leading to the activation of intracellular effecters. In addition to being associa ted with the plasma membrane, the a subunits of some of these proteins have also been localized in intracellular compartments. The mRNA of the G-prote in inhibitory a subunit 2 (G(alpha i2)) encodes two proteins, G(alpha i2) a nd sG(i2), by an alternative splicing mechanism. sG(i2) differs from G(alph a i2) in the C-terminal region and localizes in the Golgi in contrast to th e plasma membrane localization of G(alpha i2). In this paper we show that t he sequence specific to sG(i2) can direct the Gels localization of other G( alpha i) subunits, but not of the stimulatory subunit G(alpha s) or of a se creted protein. This indicates that, in addition to the sG(i2) C-terminus, sequences located elsewhere in the protein are required to determine the Go lgi localization. Inside the sG(i2) C-terminal region we have identified a 14-amino-acid proline-rich motif which specifies the Golgi localization. Fi nally, we show that the sG(i2) subunit, once activated, leaves the Gels to be localized in the endoplasmic reticulum. (C) 2000 Academic Press.