The Ubiquitin Receptor S5a/Rpn10 Links Centrosomal Proteasomes with Dendrite Development in the Mammalian Brain

Proteasomes drive the selective degradation of protein substrates with covalently linked ubiquitin chains in eukaryotes. Although proteasomes are distributed throughout the cell, specific biological functions of the proteasome in distinct subcellular locales remain largely unknown. We report that proteasomes localized at the centrosome regulate the degradation of local ubiquitin conjugates in mammalian neurons. We find that the proteasomal subunit S5a/Rpn10, a ubiquitin receptor that selects substrates for degradation, is essential for proteasomal activity at centrosomes in neurons and thereby promotes the elaboration of dendrite arbors in the rodent brain in vivo. We also find that the helix-loop-helix protein Id1 disrupts the interaction of S5a/Rpn10 with the proteasomal lid and thereby inhibits centrosomal proteasome activity and dendrite elaboration in neurons. Together, our findings define a function for a specific pool of proteasomes at the neuronal centrosome and identify a biological function for S5a/Rpn10 in the mammalian brain. [Display omitted] •The ubiquitin receptor S5a/Rpn10 promotes dendrite growth in primary neurons and in vivo•S5a/Rpn10 acts at the centrosome to regulate proteasome activity and dendrite development•The HLH protein Id1 suppresses S5a/Rpn10-dependent dendrite morphogenesis•Id1 disrupts S5a/Rpn10-mediated degradation of ubiquitin conjugates at the centrosome Although proteasomes are distributed throughout the cell, specific functions of proteasomes in distinct subcellular locales remain unknown. Here, Kim, Bonni, and colleagues report that proteasomes localized at the centrosome regulate the degradation of local ubiquitin conjugates in mammalian neurons. The ubiquitin receptor S5a/Rpn10 is essential for proteasomal activity at centrosomes and promotes dendrite growth and elaboration. They also show that the helix-loop-helix protein Id1 disrupts the interaction of S5a/Rpn10 with the proteasomal lid, thereby inhibiting centrosomal proteasome activity and dendrite elaboration.