title: Rab6, Rab8, and MICAL3 cooperate in controlling docking and fusion of exocytotic carriers.
abstract: Rab6 is a conserved small GTPase that localizes to the Golgi apparatus and cytoplasmic vesicles and controls transport and fusion of secretory carriers [1]. Another Rab implicated in trafficking from the trans-Golgi to the plasma membrane is Rab8 [2-5]. Here we show that Rab8A stably associates with exocytotic vesicles in a Rab6-dependent manner. Rab8A function is not needed for budding or motility of exocytotic carriers but is required for their docking and fusion. These processes also depend on the Rab6-interacting cortical factor ELKS [1], suggesting that Rab8A and ELKS act in the same pathway. We show that Rab8A and ELKS can be linked by MICAL3, a member of the MICAL family of flavoprotein monooxygenases [6]. Expression of a MICAL3 mutant with an inactive monooxygenase domain resulted in a strong accumulation of secretory vesicles that were docked at the cell cortex but failed to fuse with the plasma membrane, an effect that correlated with the strongly reduced mobility of MICAL3. We propose that the monooxygenase activity of MICAL3 is required to regulate its own turnover and the concomitant remodeling of vesicle-docking protein complexes in which it is engaged. Taken together, the results of our study illustrate cooperation of two Rab proteins in constitutive exocytosis and implicates a redox enzyme in this process.
authors: Department of Cell Biology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.
authors: Ilya
authors: I
authors: Grigoriev
authors: Ka Lou
authors: KL
authors: Yu
authors: Emma
authors: E
authors: Martinez-Sanchez
authors: Andrea
authors: A
authors: Serra-Marques
authors: Ihor
authors: I
authors: Smal
authors: Erik
authors: E
authors: Meijering
authors: Jeroen
authors: J
authors: Demmers
authors: Johan
authors: J
authors: Peränen
authors: R Jeroen
authors: RJ
authors: Pasterkamp
authors: Peter
authors: P
authors: van der Sluijs
authors: Casper C
authors: CC
authors: Hoogenraad
authors: Anna
authors: A
authors: Akhmanova