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Bassoon and Piccolo maintain synapse integrity by regulating protein ubiquitination and degradation
Author(s) -
Waites Clarissa L,
LealOrtiz Sergio A,
Okerlund Nathan,
Dalke Hannah,
Fejtova Anna,
Altrock Wilko D,
Gundelfinger Eckart D,
Garner Craig C
Publication year - 2013
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2013.27
Subject(s) - biology , proteostasis , synapse , microbiology and biotechnology , ubiquitin , glutamatergic , ubiquitin ligase , active zone , neuroscience , synaptic vesicle , glutamate receptor , biochemistry , receptor , vesicle , membrane , gene
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.