Ceramide Accumulation Uncovers a Cycling Pathway for the cis-Golgi Network Marker, Infectious Bronchitis Virus M Protein

Maceyka, Michael; Machamer, Carolyn E.

There are two possible mechanisms to maintain the steady-state localization of proteins to specific sites along the secretory pathway: (a) retention in the particular compartment, and (b) retrieval from other compartments (Machamer, 1993; Nilsson and Warren, 1994) . The redistribution of IBV M induced by PDMP was surprising, as we expected that if we disrupted its localization, it would move with "bulk flow" to the plasma membrane. That IBV M was redistributed to the ER suggests that it has specific targeting information for retrieval to the ER. Coupled with earlier work in our laboratory on the role of oligomerization of IBV M chimeras in CGN targeting (Weisz et al., 1993) , our findings suggest that IBV M maintains its steady-state distribution by both retention and retrieval ( Fig. 10 A) . We propose two models to explain the redistribution of IBV M protein induced by PDMP. The simplest model (Fig. 10 B, left arrow) is that the M protein normally cycles between the ER and the Golgi at a significant rate, as has been shown for ERGIC-53 (Lippincott-Schwartz et al., 1990; Schindler et al., 1993) . The slowing of anterograde traffic would cause the protein to shift its steady-state distribution to the ER, assuming that retrograde traffic is unaffected or perhaps increased by PDMP. A second possibility is that PDMP disrupts retention of the M protein, which then cycles back to the ER by normal retrieval mechanisms (Fig. 10 B, right arrow) . These two models are not mutually exclusive, and both effects of PDMP may be necessary to redistribute IBV M to the extent observed.