The Golgi-associated Hook3 protein is a member of a novel family of microtubule-binding proteins

Microtubules are central to the spatial organization of diverse membrane-tr afficking systems. Here, we report that Hook proteins constitute a novel fa mily of cytosolic coiled coil proteins that bind to organelles and to micro tubules. The conserved NH2-terminal domains of Hook proteins mediate attach ment to microtubules, whereas the more divergent COOH-terminal domains medi ate the binding to organelles. Human Hook3 bound to Golgi membranes in vitr o and was enriched in the cis-Golgi in vivo. Unlike other cis-Golgi-associa ted proteins, however. a large fraction of Hook3 maintained its juxtanuclea r localization after Brefeldin A treatment, indicating a Golgi-independent mechanism for Hook3 localization. Because overexpression of Hook3 caused fr agmentation of the Golgi complex, we propose that Hook3 participates in def ining the architecture and localization of the mammalian Golgi complex.