Intermediate filament reorganization during mitosis is mediated by p34cdc2 phosphorylation of vimentin

Y H Chou1, J R Bischoff, D Beach

  • 1Department of Cell, Molecular and Structural Biology, Northwestern University, Chicago, Illinois 60611.

Cell
|September 21, 1990
PubMed

Insights

During mitosis, intermediate filament (IF) proteins like vimentin are hyperphosphorylated by a p34cdc2 kinase complex, leading to IF network disassembly. This phosphorylation is crucial for cellular reorganization during M phase.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Intermediate filaments (IFs) depolymerize during mitosis.
  • Vimentin and desmin are hyperphosphorylated at specific sites during mitosis.
  • The kinases responsible for vimentin hyperphosphorylation are not fully characterized.

Purpose of the Study:

  • To characterize a vimentin kinase involved in mitotic IF reorganization.
  • To identify the components of the vimentin kinase complex.
  • To determine if vimentin is a substrate of p34cdc2.

Main Methods:

  • Purification of vimentin kinase activity from mitotic BHK-21 cell lysates.
  • Copurification with histone H1 kinase activity and p13suc1-Sepharose binding.
  • In vitro phosphorylation assays using purified kinase complex and vimentin.

Main Results:

  • Vimentin kinase activity copurified with histone H1 kinase and bound to p13suc1-Sepharose.
  • The purified kinase complex contained p34cdc2, 65 kDa, and 110 kDa polypeptides.
  • The kinase complex phosphorylated vimentin in vitro at mitotic sites and induced disassembly of IFs.

Conclusions:

  • Vimentin is a direct substrate of the p34cdc2 kinase complex.
  • Phosphorylation of vimentin by p34cdc2 contributes to the reorganization of the intermediate filament network during M phase.
  • This study identifies a key mechanism for mitotic cellular restructuring.

Related Concept Videos

Formation of Intermediate Filaments00:57

Formation of Intermediate Filaments

Intermediate filaments are cytoskeletal proteins with higher tensile strength and flexibility than microfilaments and microtubules. Unlike the other two cytoskeletal proteins, intermediate filament formation lacks the enzymatic activity to hydrolyze nucleotides like ATP and GTP to generate energy for polymerization. Therefore, the formation of intermediate filaments is multistep self-assembly. The involvement of any accessory proteins in intermediate filament formation has not yet been reported.
Forces Acting on Chromosomes02:11

Forces Acting on Chromosomes

During mitosis, chromosome movements occur through the interplay of multiple piconewton level forces. In prometaphase, these forces help in chromosome assembly or congression at the equatorial plane, eventually leading to their alignment at the metaphase plate. The forces acting on the chromosomes are space and time-dependent; therefore, they vary with the position of the chromosomes as the cell progresses through mitosis. 
Microtubules and motor proteins exert two types of forces on...
Separation of Sister Chromatids02:17

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
Mechanism of Filopodia Formation01:39

Mechanism of Filopodia Formation

Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Disassembly of Intermediate Filaments01:35

Disassembly of Intermediate Filaments

Intermediate filaments (IFs) do not undergo spontaneous disassembly. Enzymes, kinases, and phosphatases add and remove phosphates from specific sites to regulate their disassembly. The IF concentration in the cytoplasm also regulates the disassembly. If the concentration crosses a threshold, it activates the protein kinases in the vicinity, allowing the phosphorylation of IFs.
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
Separation of Sister Chromatids02:17

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...