Scyl1 regulates Golgi morphology.
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.


RESULTS
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
Our results place Scyl1 at an interface between the golgin network and COPI trafficking and demonstrate that Scyl1 is required for the maintenance of Golgi morphology. Coupled with the observation from others that Scyl1 is the gene product responsible for the neurodegenerative mouse model mdf, our results additionally implicate the regulation of COPI trafficking and Golgi homeostasis in neurodegeneration.
Burman
Jonathon L
JL
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Hamlin
Jason N R
JN
McPherson
Peter S
PS
D033942:Adaptor Proteins, Vesicular Transport; D000642:Ammonia-Lyases / Q000737:chemistry; D001692:Biological Transport; D002384:Catalysis; D002462:Cell Membrane / Q000378:metabolism; D020755:Coat Protein Complex I / Q000378:metabolism; D004268:DNA-Binding Proteins; D003902:Detergents / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation; D006056:Golgi Apparatus / Q000378:metabolism*; D000077614:Golgi Matrix Proteins; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000737:chemistry
D033942:Adaptor Proteins, Vesicular Transport; D020755:Coat Protein Complex I; D004268:DNA-Binding Proteins; D003902:Detergents; D000077614:Golgi Matrix Proteins; D008565:Membrane Proteins; C464929:SCYL1 protein, human; D014157:Transcription Factors; D033921:Vesicular Transport Proteins; C091580:vesicular transport factor p115; D000642:Ammonia-Lyases; C020148:formiminotetrahydrofolate cyclodeaminase