BARS is closely related to the CtBP family of transcriptional repressors needed for normal embryonic development in mouse and fly. Corda and Luini previously found that, in rat cells, BARS is what brefeldin A might target with its ADP ribosylation activity when it inhibits Golgi trafficking. Their subsequent work suggested that BARS is needed for the fission of vesicles during trafficking.
The new report indicates that BARS also cuts up the Golgi into vesicles and small tubules to be shared by daughter cells. The authors removed BARS activity from cultured rat cells using antisense methods or from an in vitro Golgi fission assay by immunodepletion or dominant-negative mutants. In all cases, Golgi stacks disassembled into a tubular network, but were not fragmented further into vesicles. The BARS-depleted cells did not enter mitosis, a known side effect of the failure to break down the Golgi.
How BARS might induce fission is unclear. Its acyl transferase activity modifies lipids such as LPA and might thus induce a needed structural change in the membrane. However, mutation of this activity reduced but did not abolish its fission activity in vitro.
Mice CtBP mutants have developmental problems, but cell cultures can be made from these lines, and architectural Golgi defects have not yet been found. “We think that BARS is the main mechanism for Golgi fission during mitosis,” says Corda, “and that there are other redundant mechanisms that can take over where BARS fails.” Fail-safes might include dynamin, which has also been proposed to cleave the Golgi. ▪