A motor goes mitotic and divorces the Golgi complex

Abstract

Use of two-hybrid screening has previously shown that the Rab6-binding kinesin Rab6-KIFL is a partner of Rab6, a Golgi-associated GTPase implicated in intra-Golgi membrane traffic. Hill et al.1xThe Rab6-binding kinesin, Rab6-KIFL, is required for cytokinesis. Hill, E. et al. EMBO J. 2000; 19: 5711–5719Crossref | PubMedSee all References1 have now characterized the expression, localization and tentative function of human Rab6-KIFL. Rab6-KIFL accumulates in mitotic HeLa cells, where it localizes to central spindle microtubules and to the midbody during cytokinesis. Using an antiserum raised against the Rab6-binding domain of Rab6-KIFL, Hill et al. demonstrate that levels of the protein oscillate in a cell-cycle-controlled manner, mirroring the behavior of cyclin B2. This suggests that Rab6-KIFL is a kinesin found solely in cells during mitosis. Most interestingly, microinjection of antibodies against Rab6-KIFL blocks cytokinesis and results in a dramatic accumulation of binucleate cells. Furthermore, overexpression of Rab6-KIFL in HeLa cells causes cell death. Thus, Rab6-KIFL might be a microtubule motor with functions during formation of the cleavage furrow and cytokinesis.These new data on Rab6-KIFL create a conundrum as we had grown accustomed to think about this protein more as a Golgi-associated motor protein involved in vesicular traffic in interphase cells 2xInteraction of a Golgi-associated kinesin-like protein with Rab6. Echard, A. et al. Science. 1998; 279: 580–585Crossref | PubMed | Scopus (349)See all References2. Echard et al.2xInteraction of a Golgi-associated kinesin-like protein with Rab6. Echard, A. et al. Science. 1998; 279: 580–585Crossref | PubMed | Scopus (349)See all References2 had demonstrated a staining of the Golgi complex in interphase HeLa cells with an antiserum raised against the same region of (mouse) Rab6-KIFL as used by Hill et al. Intriguingly, any such Golgi staining pattern is absent with the new Rab6-KIFL antiserum raised by Hill et al. There are several possible explanations for this difference. The antiserum used by Echard et al. might contain a cross-reactivity against a Golgi-associated protein that masks the real localization of Rab6-KIFL. Indeed, Hill et al. show that their antiserum recognizes only the 100-kDa band of Rab6-KIFL, whereas the antiserum raised by Echard et al. additionally sees a band of 200 kDa. However, a much more interesting possibility could perhaps be that the two laboratories have characterized highly related but functionally distinct isoforms of Rab6-KIFL that perform functions in mitotic and interphase cells, respectively. Future experiments will show us whether Rab6-KIFL has divorced the Golgi complex or whether we might yet see a reconciliation.