Augmin complex activity finetunes dendrite morphology through non-centrosomal microtubule nucleation in vivo

Abstract

During development neurons achieve a stereotyped neuron type-specific morphology, which relies on dynamic support by microtubules (MTs). An important player is augmin which binds to existing MT filaments and recruits the γ-Tubulin Ring Complex (γ-TuRC), to form branched MTs. In cultured neurons, augmin is important for neurite formation. However, little is known about the role of augmin during neurite formation in vivo. Here, we have revisited the role of mammalian augmin in culture and then turned towards the class four Drosophila dendritic arborization (c4da) neurons. We show that MT density is maintained through augmin in cooperation with the γ-TuRC in vivo. Mutant c4da neurons show a reduction of newly emerging higher-order dendritic branches and in turn also a reduced number of their characteristic space-filling higher-order branchlets. Taken together, our data reveal a cooperative function of the augmin complex with the γ-TuRC in forming enough MTs needed for the appropriate differentiation of morphologically complex dendrites in vivo.

γ-TuRCs and the augmin complex are required for the development of highly branched dendritic arbors in Drosophila

“…Based on our current data, we propose that γ-TuRCs are instead recruited via augmin to the sides of pre-existing microtubules. The role of augmin in supporting higher-order branching is also supported by a similar study published in this issue ( Zhang et al, 2024 ). There are several non-mutually exclusive possibilities for how microtubules nucleated from augmin-bound γ-TuRCs might ultimately grow within terminal dendrites.…”

Nascent dendrite branches initiated by a localized burst of Spire-dependent actin polymerization

“…In dendrites, Spir could contribute to an actin pool for myosin-V-mediated delivery of Rab11 vesicles to nascent branches, supplying lipids and proteins required for their protrusive growth. This actin pool could allow for the subsequent invasion of microtubules into these nascent branches, perhaps mediated by myosin-6 55 or augmin 56 , and the transition to microtubule-dependent long-distance transport of cargo-carrying vesicles. While further experiments are required to fully elucidate the mechanisms of dendrite branching, our findings show that Spir-mediated actin dynamics link branch initiation with protrusive outgrowth in vivo.…”

“…In dendrites, Spir could contribute to an actin pool for myosin-Vmediated delivery of Rab11 vesicles to nascent branches, supplying lipids and proteins required for their protrusive growth. This actin pool could allow for the subsequent invasion of microtubules into these nascent branches, perhaps mediated by myosin-6 55 or augmin 56…”