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Quantitative Immunofluorescence Assay to Measure the Variation in Protein Levels at Centrosomes
09:39

Quantitative Immunofluorescence Assay to Measure the Variation in Protein Levels at Centrosomes

Published on: December 20, 2014

Cdk5 phosphorylation of FAK regulates centrosome-associated miocrotubules and neuronal migration

Zhigang Xie1, Li-Huei Tsai

  • 1Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA. zhigang_xie@hms.harvard.edu

Cell Cycle (Georgetown, Tex.)
|January 9, 2004
PubMed

Insights

Cyclin-dependent kinase 5 (Cdk5) phosphorylates focal adhesion kinase (FAK) at Serine 732, regulating neuronal migration during brain development by impacting microtubule structures. This phosphorylation prevents FAK accumulation at the centrosome.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Cyclin-dependent kinase 5 (Cdk5) is crucial for neuronal development, particularly neuronal migration.
  • Focal adhesion kinase (FAK) is implicated in various cellular processes, but its role in neuronal migration is less understood.
  • Cdk5's substrates and precise regulatory mechanisms in neuronal migration require further elucidation.

Purpose of the Study:

  • To investigate the role of Cdk5 in regulating neuronal migration.
  • To identify and characterize the phosphorylation of FAK by Cdk5.
  • To elucidate the functional consequences of FAK phosphorylation at Serine 732 (S732) on neuronal migration.

Main Methods:

  • In vitro kinase assays to determine Cdk5's phosphorylation of FAK.
  • Use of phospho-specific antibodies against FAK S732.
  • Employing an S732-unphosphorylatable mutant FAK to assess functional impact in vivo.

Main Results:

  • Cdk5 directly phosphorylates FAK at S732 in vitro and in the developing brain.
  • S732 phosphorylation of FAK is essential for nuclear translocation during neuronal migration.
  • This phosphorylation regulates centrosome-associated microtubule structures and prevents FAK accumulation at the centrosome, without affecting FAK's kinase activity.

Conclusions:

  • Cdk5-mediated phosphorylation of FAK at S732 is a key regulatory mechanism for neuronal migration.
  • FAK plays a direct role in regulating microtubules via Cdk5-dependent phosphorylation.
  • This study highlights a functional similarity between Cdk5 in neuronal migration and Cdk1 in cell division.

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