Novel functions for the anaphase-promoting complex in neurobiology

Department of Pathology, Harvard Medical School, Boston, MA 02115, United States.
Seminars in Cell and Developmental Biology (Impact Factor: 6.27). 03/2011; 22(6):586-94. DOI: 10.1016/j.semcdb.2011.03.006
Source: PubMed


In recent years, diverse and unexpected neurobiological functions have been uncovered for the major cell cycle-regulated ubiquitin ligase, the anaphase-promoting complex (APC). Functions of the APC in the nervous system range from orchestrating neuronal morphogenesis and synapse development to the regulation of neuronal differentiation, survival, and metabolism. The APC acts together with the coactivating proteins Cdh1 and Cdc20 in neural cells to target specific substrates for ubiquitination and consequent degradation by the proteasome. As we continue to unravel APC functions and mechanisms in neurobiology, these studies should advance our understanding of the molecular mechanisms of neuronal connectivity, with important implications for the study of brain development and disease.

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    • "A big surprise came several years later, when the anaphase promoting complex (APC), a classical component of the cell cycle [22], was discovered to be both highly expressed in postmitotic neurons and localized to synapses [23–25]. This massive E3 complex, composed of at least 12 subunits, requires binding by Cdh1 or Cdc20 to function, allowing APC activity to be controlled in distinct subcellular compartments by either of these activator proteins [26]. The APC, specifically in conjunction with Cdh1, regulates axon length [25, 27, 28]. "
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    • "Proper regulation of APC Cdc20 may increase chromosome segregation fidelity, reducing non-disjunction events, and potentially increasing cellular healthspan. Other non-mitotic functions have now been ascribed to the APC, including maintaining neuronal development and genomic stability, as well as regulating chromatin metabolism and enhancing longevity in yeast and higher eukaryotic organisms (Harkness et al., 2002, 2004, 2005; Baker et al., 2004; Arnason et al., 2005; Turnell et al., 2005; Li et al., 2008; Turner et al., 2010; Eguren et al., 2011; Islam et al., 2011; Puram and Bonni, 2011; Postnikoff et al., 2012). As diverse as APC functions seem to be, regulatory mechanisms controlling APC output remain largely unknown. "
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