Distinct Sets of Rab6 Effectors Contribute to <scp>ZW10</scp>‐ and <scp>COG</scp>‐Dependent Golgi Homeostasis

<jats:p>The organization of the Golgi apparatus is determined in part by the interaction of Rab proteins and their diverse array of effectors. Here, we used multiple approaches to identify and characterize a small subset of effectors that mimicked the effects of Rab6 on Golgi ribbon organization. In a visual‐based, candidate protein screen, we found that the individual depletion of any of three Rab6 effectors, myosin <jats:styled-content style="fixed-case">IIA</jats:styled-content> (<jats:styled-content style="fixed-case">MyoIIA</jats:styled-content>), <jats:styled-content style="fixed-case">Kif20A</jats:styled-content> and Bicaudal D (<jats:styled-content style="fixed-case">BicD</jats:styled-content>), was sufficient to suppress Golgi ribbon fragmentation/dispersal coupled to retrograde tether proteins in a manner paralleling Rab6. <jats:styled-content style="fixed-case">MyoIIA</jats:styled-content> and <jats:styled-content style="fixed-case">Kif20A</jats:styled-content> depletions were pathway selective and suppressed <jats:styled-content style="fixed-case">ZW10</jats:styled-content>‐dependent Golgi ribbon fragmentation/dispersal only whereas <jats:styled-content style="fixed-case">BicD</jats:styled-content> depletion, like Rab6, suppressed both <jats:styled-content style="fixed-case">ZW10</jats:styled-content>‐ and <jats:styled-content style="fixed-case">COG</jats:styled-content>‐dependent Golgi ribbon fragmentation. The <jats:styled-content style="fixed-case">MyoIIA</jats:styled-content> effects could be produced in short‐term assays by the reversible myosin inhibitor, blebbistatin. At the electron microscope level, the effects of <jats:styled-content style="fixed-case">BicD</jats:styled-content>‐depletion mimicked many of those of Rab6‐depletion: longer and more continuous Golgi cisternae and a pronounced accumulation of coated vesicles. Functionally, <jats:styled-content style="fixed-case">BicD</jats:styled-content>‐depleted cells were inhibited in transport of newly synthesized <jats:styled-content style="fixed-case">VSV</jats:styled-content>‐G protein to the cell surface. In summary, our results indicate small, partially overlapping subsets of Rab6 effectors are differentially important to two tether‐dependent pathways essential to Golgi organization and function.</jats:p><jats:p><jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/tra12167-gra-0001.gif" xlink:title="image"/></jats:p>