Activity produces waste, so it makes sense to position waste disposal facilities close to sites of activity. Baris Bingol and Erin Schuman (California Institute of Technology, Pasadena, CA) have discovered that neurons do just that, recruiting proteasomes to active dendritic spines.
Dendritic spines must construct and destroy many proteins as they respond to synaptic excitation. Protein synthesis machinery has been shown to sit locally in spines to make protein when needed. Indication that the degradation machinery (proteasomes) might also serve its function locally came from Bingol's discovery that adjacent synapses in the same neuron contained different amounts of proteasome.
Investigating the dynamics of this varied distribution, the team observed that excitation of neurons drove proteasomes from the shafts to the spines within minutes. Proteasome levels then remained high in the spines for up to an hour. Ubiquitinated proteins, targeted for destruction, also initially increased, but shortly thereafter decreased as the proteasomes arrived and got to work. Thus, the study shows that proteasomes are dynamic machines that are capable of moving toward their targets.
The increase in spine proteasome levels was due partly to recruitment and mostly to sequestration, and excitation led to an increased association of proteasomes with the actin cytoskeleton, suggesting a possible mechanism for activity-dependent localization. Investigating the molecular mechanics of actin binding would be the sensible next step, says Bingol.