Polo-like kinases in the nervous system

Polo like kinases (Plks) are key regulators of the cell cycle, but little is known about their functions in postmitotic cells such as neurons. Recent findings indicate that Plk2 and Plk3 are dynamically regulated in neurons by synaptic activity at the mRNA and protein levels. In COS cells, Plk2 and Plk3 interact with spine-associated Rap guanosine triphosphatase-activating protein (SPAR), a regulator of actin dynamics and dendritic spine morphology, leading to its degradation through the ubiquitin-proteasome system. Induction of Plk2 in hippocampal neurons eliminates SPAR protein, depletes a core postsynaptic scaffolding molecule (PSD-95), and causes loss of mature dendritic spines and synapses. These findings implicate neuronal Plks as mediators of activity-dependent change in molecular composition and morphology of synapses. Induction of Plks might provide a homeostatic mechanism for global dampening of synaptic strength following heightened neuronal activity ('synaptic scaling'). Synapse-specific actions of induced Plks are also possible, particularly in light of the discovery of phosphoserine/threonine peptide motifs as binding targets of the polo box domain, which could allow for 'priming' phosphorylation by upstream kinases that could 'tag' Plk substrates only in specific synapses.