Figure 5.

Various subnetworks of signaling molecules that regulate Golgi structure. (A) Phosphatidylinositol (PI) network regulators identified in the screen. Depletion of either PIK4CA or PIK4CB resulted in a highly diffuse and fragmented Golgi. PIP4 is possibly converted into PI4,5P by PIP5K1A as indicated by fragmentation of the Golgi upon knockdown. Depletion of PTEN, the phosphatase for PI3,4,5P, exhibited a condensed Golgi phenotype. Diacylglycerol (DAG), a downstream product of PI4,5P is converted into phosphatidic acid (PA) by DGKZ whose knockdown resulted in a fragmented Golgi. Different PI species can recruit various membrane trafficking effectors (green nodes). (B) Regulators of the actomyosin machinery also regulate Golgi organization. ROCK1 depletion resulted in a compact Golgi while PAK1 depletion resulted in a fragmented Golgi. (C) Link between cell-cycle kinases and trans Golgi-plasma membrane trafficking. Knockdown of mitotic checkpoint kinase BUB1 and cell-cycle control kinase CDC2 resulted in a specifically trans diffuse Golgi. (D) Multiple players from different tiers of the MAP kinase signaling pathway appear as hits in our screen and the screen by Farhan et al (2010), highlighting the importance of MAP kinases in the regulation of the secretory system. Tiers of the MAP kinase pathway are indicated on the left and the four main MAP kinase pathways are indicated at the top. Dark green nodes and light green nodes represent phosphorylated Golgi proteins and Golgi proteins, respectively. Orange nodes represent hit genes from Farhan et al (2010). Grey nodes represent non-hit genes in both screens. Red arrows indicate phosphorylation. Black arrows indicate non-phosphorylation based activation. Dashed lines indicate recruitment. Purple lines indicate confirmed protein–protein interaction curated in HPRD database. Black lines indicate protein–protein interaction based on the STRING database.