ERK1c regulates Golgi fragmentation during mitosis

Abstract

Extracellular signal-regulated kinases (ERK) are signaling molecules that regulate a wide array of cellular processes. Recently we cloned an alternatively spliced isoform of ERK1, named ERK1c, and demonstrated that it is regulated differently from other ERKs upon various stimulations. In addition, we showed that this isoform can be found in the Golgi apparatus under distinct conditions. This led to our working hypothesis stating that ERK1c participates in the regulation of mitotic Golgi fragmentation, which is known to be mediated by MEK1 without the involvement of ERK1/2. Therefore, the Objective of the work was to study the function of ERK1c in the Golgi during mitosis. Using FACS analysis, SiRNA, and immunofluorescence technique, our results show that during late G2 phase and mitosis, ERK1c expression and activation, were increased and ERK1c translocated to the Golgi complex. ERK1c knockdown with specific SiRNA resulted in a significant attenuation of Golgi fragmentation and consequently also of mitotic progression, whereas overexpressed ERK1c facilitated these processes. Modulation of MEK1 activity during mitosis affected ERK1c activity as well as Golgi fragmentation, while changes in ERK1/2 levels did not affect these processes, suggesting that MEK1 facilitates the Golgi fragmentation specifically by ERK1c. We concluded that ERK1c is a unique MEK effector that extends the specificity of the ERK signaling cascade to regulate Golgi fragmentation. Therefore, alternatively spliced isoforms can serve as a mean for determining the specificity of the ERK cascade that is known to regulate different and even opposing cellular processes. Research support: Israel Cancer Association