Role of Diacylglycerol in PKD Recruitment to the TGN and Protein Transport to the Plasma Membrane

Abstract

Protein kinase D (PKD) is a cytosolic serine-threonine kinase that binds to the trans-Golgi network (TGN) and regulates the fission of transport carriers specifically destined to the cell surface. PKD was found to bind diacylglycerol (DAG), and this binding was necessary for its recruitment to the TGN. Reducing cellular levels of DAG inhibited PKD recruitment and blocked protein transport from the TGN to the cell surface. Thus, a DAG-dependent, PKD-mediated signaling regulates the formation of transport carriers from the TGN in mammalian cells.

Protein kinase D1/2 is involved in the maturation of multivesicular bodies and secretion of exosomes in T and B lymphocytes

“…[10][11][12][13][14][15] The discovery of exosome involvement in these responses increased interest in the regulation of exosome biogenesis and secretory traffic, with special attention to the contribution of lipids such as ceramide and DAG, as well as DAG-binding proteins. 14,[16][17][18][19][20][21] These studies suggest that positive and negative DAG regulators may control secretory traffic. By transforming DAG into phosphatidic acid (PA), diacylglycerol kinase α (DGKα) is essential for the negative control of DAG function in T lymphocytes.…”

“…23,24 The secretory vesicle pathway involves several DAGcontrolled checkpoints at which DGKα may act; these include vesicle formation and fission at the trans-Golgi network (TGN), MVB maturation, as well as their transport, docking and fusion to the plasma membrane. 9,[16][17][18][19][20] The molecular components that regulate some of these trafficking processes include protein kinase D (PKD) family members. 21 PKD1 activity, for instance, regulates fission of transport vesicles from TGN via direct interaction with the pre-existing DAG pool at this site.…”

“…21 PKD1 activity, for instance, regulates fission of transport vesicles from TGN via direct interaction with the pre-existing DAG pool at this site. 19 The cytosolic serine/threonine kinases PKD1, PKD2 and PKD3 (ref. 21) are expressed in a wide range of cells, with PKD2 the most abundant isotype in T lymphocytes.…”

“…27 Based on our previous studies showing DGKα regulation of DAG in MVB formation and exosome secretion, 9,14,28 and the identification of PKD1/2 association to MVB, 14 we hypothesized that DGKα control of DAG mediates these events, at least in part, through PKD. Here we explored whether, in addition to its role in vesicle fission from TGN, 19 PKD regulates other steps in the DAG-controlled secretory traffic pathway. Using PKD-deficient cell models, we analyzed the role of PKD1/2 in MVB formation and function, and demonstrate their implication in exosome secretory traffic.…”

Protein kinase D: a new player among the signaling proteins that regulate functions in the nervous system

“…As no interactions have been found between the PH domain of PKD1 and phosphorylated inositol lipids, which are important ligands responsible for membrane localization, this domain is not required for plasma membrane translocation [31,32] or Golgi localization [33][34][35][36][37][38][39] like other PH-domain-containing AGC kinases, such as PKB and the GRKs. However, the PH domain is required for the nuclear export of PKD1 [22,40] .…”