A region containing a proline-rich motif targets sGi2 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 associated with the plasma membrane, the a subunits of some of these proteins have also been localized in intracellular compartments. The mRNA of the G-protein inhibitory a subunit 2 (G(alpha i2)) encodes two proteins, G(alpha i2) and sG(i2), by an alternative splicing mechanism. sG(i2) differs from G(alpha i2) in the C-terminal region and localizes in the Golgi in contrast to the plasma membrane localization of G(alpha i2). In this paper we show that the sequence specific to sG(i2) can direct the Golgis localization of other G(alpha i) subunits, but not of the stimulatory subunit G(alpha s) or of a secreted protein. This indicates that, in addition to the sG(i2) C-terminus, sequences located elsewhere in the protein are required to determine the Golgi localization. Inside the sG(i2) C-terminal region we have identified a 14-amino-acid proline-rich motif which specifies the Golgi localization. Finally, we show that the sG(i2) subunit, once activated, leaves the Golgi to be localized in the endoplasmic reticulum. (C) 2000 Academic Press.