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Spatial and Temporal Analysis of Active ERK in the C. elegans Germline
Published on: November 29, 2016
Analysis of ERK3 intracellular localization: dynamic distribution during mitosis and apoptosis
F Aredia1, M Malatesta, P Veneroni
1Istituto di Genetica Molecolare CNR; Università di Pavia. francesca.aredia@gmail.com.
Abstract:
Extracellular signal-regulated kinases (ERK) 1, 2 and 3 are involved in cell proliferation and differentiation, and apoptosis; although ERK1/2 have been widely studied, limited knowledge on ERK3 is available. The present work aimed at investigating ERK3 distribution during cell cycle and apoptosis in human tumor HeLa cells. The analysis performed by double immunofluorescence and immunoelectron microscopy experiments revealed that during interphase ERK3 is mainly resident in the nucleoplasm in association with ribonuclear proteins involved in early pre-mRNA splicing, it undergoes cell cycle-dependent redistribution and, during apoptosis, it remains in the nucleus in the form of massive nuclear aggregates, then moves to the cytoplasm and is finally extruded.
Insights
Extracellular signal-regulated kinase 3 (ERK3) primarily localizes to the nucleoplasm during interphase. During apoptosis, ERK3 forms nuclear aggregates before cytoplasmic translocation and extrusion.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Extracellular signal-regulated kinases (ERK) are crucial regulators of cellular processes like proliferation, differentiation, and apoptosis.
- While ERK1/2 are well-characterized, the specific functions and localization of ERK3 remain largely unknown.
- Understanding ERK3's role is vital for comprehending cell cycle regulation and apoptotic pathways.
Purpose of the Study:
- To investigate the subcellular localization and dynamic behavior of ERK3 during the cell cycle.
- To examine the distribution of ERK3 in human tumor cells undergoing apoptosis.
- To elucidate the potential involvement of ERK3 in pre-mRNA splicing and nuclear organization.
Main Methods:
- Double immunofluorescence microscopy to visualize ERK3 localization.
- Immunoelectron microscopy for high-resolution ultrastructural analysis.
- Utilized human tumor HeLa cells as a model system.
Main Results:
- During interphase, ERK3 predominantly resides in the nucleoplasm, associated with ribonuclear proteins involved in early pre-mRNA splicing.
- ERK3 exhibits cell cycle-dependent redistribution within the nucleus.
- Upon induction of apoptosis, ERK3 forms significant nuclear aggregates, subsequently translocates to the cytoplasm, and is ultimately extruded from the cell.
Conclusions:
- ERK3 plays a dynamic role in the nucleus, potentially linked to pre-mRNA splicing.
- ERK3 localization is tightly regulated throughout the cell cycle and dramatically altered during apoptosis.
- The observed nuclear aggregation and subsequent extrusion of ERK3 during apoptosis suggest a novel role in this process.
