APC/C regulation of axonal growth and synaptic functions in postmitotic neurons: the Liprin-${\varvec \alpha}$ connection

Abstract.

Protein ubiquitination has critical roles in neuronal physiology and defects in protein ubiquitination have been implicated in neurodegenerative pathology. The anaphase-promoting complex/cyclosome (APC/C) is one of two key E3 ubiquitin ligase complexes that functions in regulating cell cycle transitions in proliferating cells by acting on cyclins and components of the mitotic/meiotic apparatus. Documentation of APC/C’s action beyond cell division is sparse. In the past year, however, novel and surprising roles for APC/C in postmitotic neurons, particularly in the modulation of axonal growth and synaptic functions, have been revealed. APC/C and its activator Cdh-1 are found in good abundance in neurons, and these seem to function at different cellular locations, modulating apparently diverse processes such as axonal growth and synaptic function. Interestingly, there also appears to be a single link to these apparently divergent actions of APC/C in neurons – the multi-domain, multi-functional scaffolding protein Liprin- ${\varvec \alpha},$ which is an APC/C substrate.