Regulation of Oxysterol-binding Protein Golgi Localization through Protein Kinase D–mediated Phosphorylation

Abstract

Protein kinase D (PKD) is a critical regulator of Golgi structure and function. Biochemical evidence is presented that demonstrates the oxysterol-binding protein OSBP as a novel PKD substrate. Phosphorylation inhibits OSBP Golgi localization, impairs CERT Golgi localization, and promotes Golgi fragmentation.

Protein Kinase D Negatively Regulates Hepatitis C Virus Secretion through Phosphorylation of Oxysterol-binding Protein and Ceramide Transfer Protein

“…As we have discussed above, both CERT and OSBP positively contribute to HCV maturation/secretion (24,25). Recent reports show that PKD phosphorylates OSBP at Ser 240 and CERT at Ser 132 and inhibits their activity (phosphorylation inhibition) (31,32). We speculated that PKD1 negatively impacts HCV secretion through phosphorylation inactivation of CERT and OSBP.…”

“…At the TGN, PKD activates PI4KIII␤ to generate PI4P, which mediates the Golgi localization of CERT and OSBP proteins via binding to their pleckstrin homology (PH) domains. PKD-mediated phosphorylation of CERT at Ser 132 and OSBP at Ser 240 impairs their Golgi localization and inhibits their functions in integrating the cholesterol and sphingomyelin (SM) metabolism (31,32). Although active PKD is known to promote secretion of small cargo proteins (e.g.…”

PKD Regulates Membrane Fission to Generate TGN to Cell Surface Transport Carriers

“…The timing of the conversion of DAG into PA and/ or LPA could thus be used to regulate the dimensions of the transport carrier. The carrier formation is terminated by PKD dependent phosphorylation of OSBP and CERT and their dissociation from the TGN as reported (Fugmann et al 2007;Nhek et al 2010). Although the DAG-PKD domain is used for the generation of basolaterally targeted transport carriers, the SM-and cholesterol-enriched domain would be used for the generation of carriers containing the apically targeted cargo (Nhek et al 2010).…”

Role of Phosphatidylinositol 4-Phosphate (PI4P) and Its Binding Protein GOLPH3 in Hepatitis C Virus Secretion

“…The PI4P-binding proteins OSBP and CERT that function in the Golgi trafficking were shown to affect HCV secretion (34,35,46,47). To investigate the functional role of Golgi-localized PI4P in the HCV secretion process, we used a mutant version of the hSac1 protein, hSac1 K2A.…”