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Interaction between LIS1 and PDE4, and its role in cytoplasmic dynein function
Hannah Murdoch1, Suryakiran Vadrevu, Anke Prinz
1Molecular Pharmacology Group, Davidson/Wolfson Link Bldgs, Institute of Neuroscience and Psychology, University of Glasgow, University Avenue, Glasgow G128QQ, UK. hannah.murdoch@glasgow.ac.uk
Journal of Cell Science
|June 10, 2011
Summary
cAMP phosphodiesterase 4 (PDE4) regulates cell motility by binding LIS1, a protein crucial for cytoplasmic dynein motor function. PDE4 sequesters LIS1, impairing dynein, especially when PDE4 is phosphorylated by protein kinase A.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- LIS1 is a scaffold protein essential for cytoplasmic dynein motor function and cell motility.
- Cytoplasmic dynein drives microtubule-dependent processes, including cell migration.
Purpose of the Study:
- To investigate the interaction between LIS1 and cAMP-specific phosphodiesterases (PDE4).
- To elucidate the role of PDE4 in regulating dynein motor function and cell motility.
Main Methods:
- Biochemical assays to detect direct binding between PDE4 and LIS1.
- Functional assays measuring microtubule transport and cell migration.
- Investigating the role of protein kinase A (PKA) phosphorylation and cAMP levels.
Main Results:
- PDE4 directly binds to LIS1.
- Dissociation of LIS1 from dynein leads to impaired dynein function and cell migration.
- Upregulation of PDE4 sequesters LIS1, reducing dynein activity.
- PKA-mediated phosphorylation of long PDE4 isoforms enhances LIS1 binding, particularly under increased cAMP levels.
Conclusions:
- PDE4 acts as a novel regulator of dynein motor function by competing with dynein for LIS1 binding.
- PDE4's regulatory role is independent of its catalytic activity, highlighting a signaling function.
- This mechanism, modulated by PKA and cAMP, offers new insights into the control of cell motility.
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