Scyl1 scaffolds class II Arfs to specific subcomplexes of coatomer through the γ-COP appendage domain.
Coatomer (COPI)-coated vesicles mediate membrane trafficking in the early secretory pathway. There are at least three subclasses of COPI coats and two classes of Arf GTPases that couple COPI coat proteins to membranes. Whether mechanisms exist to link specific Arfs to specific COPI subcomplexes is unknown. We now demonstrate that Scy1-like protein 1 (Scyl1), a member of the Scy1-like family of catalytically inactive protein kinases, oligomerizes through centrally located HEAT repeats and uses a C-terminal RKXX-COO(-) motif to interact directly with the appendage domain of coatomer subunit γ-2 (also known as COPG2 or γ2-COP). Through a distinct site, Scyl1 interacts selectively with class II Arfs, notably Arf4, thus linking class II Arfs to γ2-bearing COPI subcomplexes. Therefore, Scyl1 functions as a scaffold for key components of COPI coats, and disruption of the scaffolding function of Scyl1 causes tubulation of the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) and the cis-Golgi, similar to that observed following the loss of Arf and Arf-guanine-nucleotide-exchange factor (GEF) function. Our data reveal that Scyl1 is a key organizer of a subset of the COPI machinery.
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.
Jason N R
JN
Hamlin
Lena K
LK
Schroeder
Maryam
M
Fotouhi
Hatem
H
Dokainish
Maria S
MS
Ioannou
Martine
M
Girard
Nathan
N
Summerfeldt
Paul
P
Melançon
Peter S
PS
McPherson
D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D001665:Binding Sites; D020755:Coat Protein Complex I / Q000378:metabolism*; D020756:Coatomer Protein / Q000378:metabolism*; D004268:DNA-Binding Proteins; D006056:Golgi Apparatus / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D021381:Protein Transport; D014157:Transcription Factors / Q000378:metabolism*
D033942:Adaptor Proteins, Vesicular Transport; D020755:Coat Protein Complex I; D020756:Coatomer Protein; D004268:DNA-Binding Proteins; C464929:SCYL1 protein, human; D014157:Transcription Factors
Arf4; Coatomer; ERGIC-53; Early secretory pathway; Scyl1; Tubulation; γ-COP