Localization and targeting of the Saccharomyces cerevisiae Kre2p/Mnt1p alpha 1,2-mannosyltransferase to a medial-Golgi compartment

The presence or requirement of more than one specific targeting signal in a given secretory pathway membraneassociated protein has been hinted at in a few cases recently. The TMD might not be the sole targeting motif present in particular animal glycosyltransferases as some cytoplasmic and luminal sequences appear to be involved in retention (Munro, 1991; Burke et al., 1992; Shaper and Shaper, 1992; Dahdal et al., 1993; Burke et al., 1994; Gleeson et al., 1994; Low and Hong, 1994) . The trans-Golgi network protein TGN38 appears to achieve proper Golgi localization using two nonoverlapping targeting domains: a tyrosine-based cytoplasmic retrieval signal and a retention signal found in its membrane spanning domain (Bos et al., 1993; Humphrey et al., 1993; Wong and Hong, 1993; Ponnambalam et al., 1994) . For the CGN Sed5p syntaxin, the intracellular localization is only partially specified by its TMD and an additional localization signal involving its cytoplasmic domain appears to be involved (Banfield et al., 1994) . Targeting studies on the p63 type II membrane protein indicate that the cytoplasmic, membrane-spanning and luminal domains are all necessary for proper ER-Golgi intermediate compartment localization (Hauri and Schweizer, 1992; Schweizer et al., 1993 Schweizer et al., , 1994 . Finally, the Wbpl type I membrane protein of the yeast ER possesses a cytoplasmic KKXX Golgi-to-ER retrieval motif. When this targeting motif is inactivated, Wbpl is still ER retained indicating that another targeting signal is present in the protein (Gaynor et al., 1994) .