Rab1 GTPases participate in regulating the vesicular transport of ER-Golgi compartments. Recently, GM 130, p 115, and Golgin-84 were identified as effectors of the active conformation of rab1. Here, we describe a novel protein, MICAL-1b, a splice variant of the MICAL-1a protein. Using the yeast two-hybrid system, we showed that it specifically interacts with rab1 in a nucleotide-dependent manner. The interaction was confirmed by GST pulldown experiments. Cell fractionation revealed that in contrast to the mainly membrane-associated rab 1 effector GM 130, MICAL-1 displays a predominantly cytosolic localization. We mapped the rab I interacting domain to the C-terminus of MICAL-1, which also mediates binding to the intermediate filament vimentin. Therefore, the interaction of MICAL-1 and rab 1 might provide a link between the Golgi apparatus and the intermediate filament cytoskeleton. We suggest that MICAL-1 isoforms with their multidomain structure are novel rab1 interacting proteins that function as scaffold proteins connecting different components in the cell. (C) 2003 Elsevier Science (USA). All rights reserved.