Neurofilament phosphorylation: a new look at regulation and function

Dynamic remodeling of cytoskeleton architecture is necessary for axonal growth and guidance, signal transduction and other fundamental aspects of neuron function. Protein phosphorylation plays a key part in these remodeling processes. Since neurofilaments are major cytoskeletal constituents and are among the most highly phosphorylated neuronal proteins, the control of their behavior serves as a possible model for understanding how phosphorylation regulates the many other phosphoproteins in the cytoskeleton. Recent studies show that neurofilament protein subunits are phosphorylated on both their amino-terminal head domains and carboxy-terminal tails by different protein kinases. This review considers the implications of this complex regulation for neurofilament function in normal neurons and in disease states characterized by neurofibrillary pathology.