Pruning morphologically resembles axonal or dendritic degeneration following neurological diseases or injury. In the peripheral nervous system (PNS), some dendritic arborization (da) neurons, including class I da (ddaD/ddaE) and class IV da (C4da or ddaC) neurons, prune away all their larval dendrites but leave their axons intact ( Williams and Truman, 2005 Kuo et al., 2005), whereas class III da neurons (ddaA/ddaF) are eliminated via apoptosis during the first day of metamorphosis ( Williams and Truman, 2005). In the central nervous system (CNS), mushroom body (MB) γ neurons prune their dorsal and medial axon branches as well as entire dendrites, and subsequently re-extend the medial branches to be part of the adult-specific circuits ( Lee et al., 1999). In invertebrates, such as Drosophila, the nervous systems undergo large-scale remodeling during metamorphosis, a transition from larval to adult stage ( Yu and Schuldiner, 2014 Kanamori et al., 2015). Defects in neuronal pruning result in larger dendritic spine density in layer V pyramidal neurons of autism spectrum disorder (ASD) patients ( Tang et al., 2014). In vertebrates, various cortical, hippocampal and motor neurons prune their excessive neurites and re-wire into mature circuits. After pruning, neurons often continue to extend their axons or dendrites to form the mature and functional connections. Pruning is a developmental process referred to as selective removal of unwanted neurites, for example axons, dendrites, or synapses, without causing neuronal death. In the developing nervous systems, neurons often undergo remodeling events, such as apoptosis, pruning and regrowth, which are pivotal for the refinement of mature neural circuits in both vertebrates and invertebrates ( Luo and O'Leary, 2005 Riccomagno and Kolodkin, 2015). The Reviewing Editor's assessment is that minor issues remain unresolved (see decision letter). Thus, our study demonstrates that Patronin orients minus-end-out MT arrays in dendrites to promote dendrite-specific pruning mainly through antagonizing Klp10A activity.Įditorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. Consistently, attenuation of Klp10A MT depolymerase in patronin mutant neurons significantly restored minus-end-out MTs in dendrites and thereby rescued dendrite-pruning defects. Moreover, we show that both patronin knockdown and overexpression resulted in a drastic decrease of MT minus ends and a concomitant increase of plus-end-out MTs in ddaC dendrites, suggesting that Patronin stabilizes dendritic minus-end-out MTs. The CKK domain is important for Patronin’s function in dendrite pruning. Here, we identified Patronin, a minus-end-binding protein, for its crucial and dose-sensitive role in ddaC dendrite pruning. However, a requirement of MT minus-end-binding proteins in dendrite-specific pruning remains completely unknown. ddaCs distribute the minus ends of microtubules (MTs) to dendrites but the plus ends to axons. Class IV ddaC neurons specifically prune larval dendrites without affecting axons during Drosophila metamorphosis.
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