scyl1 regulates golgi morphologyscyl1调节高尔基体形态.pdfVIP

Scyl1 Regulates Golgi Morphology ¤ Jonathon L. Burman , Jason N. R. Hamlin, Peter S. McPherson* Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada Abstract Background: Membrane trafficking is a defining feature of eukaryotic cells, and is essential for the maintenance of organelle homeostasis and identity. We previously identified Scy1-like 1 (Scyl1), a member of the Scy1-like family of catalytically inactive protein kinases, as a high-affinity binding partner of COPI coats. COPI-coated vesicles control Golgi to endoplasmic reticulum trafficking and we observed that disruption of Scyl1 function leads to a decrease in trafficking of the KDEL receptor via the COPI pathway. We reasoned that if Scyl1 plays a major role in COPI trafficking its disruption could influence Golgi homeostasis. Methodology/Principal Findings: We performed Scyl1 knock down in cultured cells using previously established methods and observed an alteration in Golgi morphology. Both the surface area and volume of the Golgi is increased in Scyl1- depleted cells, but the continuity and polarity of the organelle is unperturbed. At the ultrastructural level we observe a decrease in the orderly structure of the Golgi with an increase in cisternal luminal width, while the number of Golgi cisternae remains unchanged. The golgin family of proteins forms a detergent resistant network that controls Golgi homeostasis. Disruption of this protein network by knock down of the golgin p115 disrupts the Golgi localization of Scyl1. Moreover, we find that Scyl1 interacts with 58K/formiminotransferase cyclodeaminase (FTCD), a protein that is tightly associated with the cis face of the Golgi. Conclusions/Significance: Our results place Scyl1 at an