GRASP55 regulates Golgi ribbon formation.
Recent work indicates that mitogen-activated protein kinase kinase (MEK)1 signaling at the G2/M cell cycle transition unlinks the contiguous mammalian Golgi apparatus and that this regulates cell cycle progression. Here, we sought to determine the role in this pathway of Golgi reassembly protein (GRASP)55, a Golgi-localized target of MEK/extracellular signal-regulated kinase (ERK) phosphorylation at mitosis. In support of the hypothesis that GRASP55 is inhibited in late G2 phase, causing unlinking of the Golgi ribbon, we found that HeLa cells depleted of GRASP55 show a fragmented Golgi similar to control cells arrested in G2 phase. In the absence of GRASP55, Golgi stack length is shortened but Golgi stacking, compartmentalization, and transport seem normal. Absence of GRASP55 was also sufficient to suppress the requirement for MEK1 in the G2/M transition, a requirement that we previously found depends on an intact Golgi ribbon. Furthermore, mimicking mitotic phosphorylation of GRASP55 by using aspartic acid substitutions is sufficient to unlink the Golgi apparatus in a gene replacement assay. Our results implicate MEK1/ERK regulation of GRASP55-mediated Golgi linking as a control point in cell cycle progression.
Feinstein
Timothy N
TN
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Linstedt
Adam D
AD
D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D006056:Golgi Apparatus / Q000378:metabolism*; D000077614:Golgi Matrix Proteins; D006367:HeLa Cells; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D046529:Microscopy, Electron, Transmission; D008938:Mitosis; D008954:Models, Biological; D010766:Phosphorylation; D014162:Transfection
C108705:GORASP1 protein, human; C122048:GORASP2 protein, human; D000077614:Golgi Matrix Proteins; D008565:Membrane Proteins; D016203:CDC2 Protein Kinase; D048049:Extracellular Signal-Regulated MAP Kinases