Bassoon and Piccolo maintain synapse integrity by regulating protein ubiquitination and degradation

EMBO J. 2013 Apr 3;32(7):954-69. doi: 10.1038/emboj.2013.27. Epub 2013 Feb 12.


The presynaptic active zone (AZ) is a specialized microdomain designed for the efficient and repetitive release of neurotransmitter. Bassoon and Piccolo are two high molecular weight components of the AZ, with hypothesized roles in its assembly and structural maintenance. However, glutamatergic synapses lacking either protein exhibit relatively minor defects, presumably due to their significant functional redundancy. In the present study, we have used interference RNAs to eliminate both proteins from glutamatergic synapses, and find that they are essential for maintaining synaptic integrity. Loss of Bassoon and Piccolo leads to the aberrant degradation of multiple presynaptic proteins, culminating in synapse degeneration. This phenotype is mediated in part by the E3 ubiquitin ligase Siah1, an interacting partner of Bassoon and Piccolo whose activity is negatively regulated by their conserved zinc finger domains. Our findings demonstrate a novel role for Bassoon and Piccolo as critical regulators of presynaptic ubiquitination and proteostasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Mice
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Presynaptic Terminals / metabolism*
  • Proteolysis*
  • RNA Interference
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination / physiology*
  • Zinc Fingers


  • Bsn protein, mouse
  • Bsn protein, rat
  • Cytoskeletal Proteins
  • Nerve Tissue Proteins
  • Neuropeptides
  • Pclo protein, mouse
  • Pclo protein, rat
  • Ubiquitin-Protein Ligases