Sci. STKE, 30 November 2004
NEUROBIOLOGY APC, Not Just for Anaphase Anymore
Control of protein abundance through ubiquitin-dependent protein degradation has been implicated in the regulation of neuronal synaptic plasticity, but the responsible molecular machinery has not been identified. Van Roessel et al. demonstrate a role for the anaphase-promoting complex or cyclosome (APC), a multisubunit ubiquitin ligase better known for its role in control of the cell cycle, where it degrades mitotic cyclins and inhibitors of chromosome segregation to promote completion of mitosis. Drosophila mutants lacking APC function showed enlarged neuromuscular synapses. Targeted expression of APC in neurons (but not in muscle) restored more normal synaptic size. APC components were detected at neuromuscular junctions by immunofluorescence microscopy. A search for possible substrates that contained sequence motifs recognized by APC targeting subunits that also have effects on synaptic size or function revealed Liprin-α, a protein that interacts with Dlar, a protein tyrosine phosphatase. Indeed, the effects of APC on neuromuscular junctions appear to be mediated by Lipren-α because loss of one copy of the Drosophila Liprin gene suppressed the phenotype of APC mutant. The magnitude of excitatory potentials at neuromuscular junctions was also increased in APC mutants, apparently mediated by an increase in the abundance of glutamate receptors at the synapses. Along with recent evidence that the APC suppresses axonal growth in rat brain, the findings that the APC also regulates synaptic growth and transmission confirm that postmitotic neurons put APC complexes to good use.
P. van Roessel, D. A. Elliott, I. M. Robinson, A. Prokop, A. H. Brand, Independent regulation of synaptic size and activity by the anaphase-promoting complex. Cell 119, 707-718 (2004). [Online Journal]
Citation: APC, Not Just for Anaphase Anymore. Sci. STKE 2004, tw436 (2004).
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