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Rumpf, S.

Publications and source records attributed to Rumpf, S..

3 recordsLinked to original sources

The UAP56 mRNA Export Factor is Required for Dendrite and Synapse Pruning via Actin Regulation in Drosophila

Neurite and synapse pruning are conserved mechanisms that adapt neuronal circuitry to different developmental stages. Drosophila sensory c4da neurons prune their larval dendrites and their presynaptic terminals during metamorphosis using a gene expression programme that is induced by the steroid hormone ecdysone and involves posttranscriptional regulation pathways. Here we show that loss of the helicase UAP56, an important mediator of nuclear mRNA export, causes strong dendrite and presynapse pruning defects. Loss of UAP56 is linked to actin regulation, as it causes defects in the expression of the actin severing enzyme Mical during dendrite pruning, and actin accumulation at presynapses, where cofilin is required for pruning. Our findings suggest specificity in mRNA export pathways and identify a role for actin disassembly during presynapse pruning.

neuroscience↗

Spectraplakin cooperates with noncentrosomal microtubule regulators to orient dendritic microtubules in Drosophila

The differential microtubule organization in axons and dendrites underlies neuronal polarity and developmental processes like neurite pruning. How neurons achieve their specific microtubule organization during development is an area of active research, and it has been especially hard to explain how dendritic microtubules are oriented with their plus ends towards the soma. Transient microtubule nucleation from tips of early growing dendrites has been detected in some systems and would explain how orientation is set up. In a survey for cytoskeletal regulators involved in dendrite pruning and microtubule organization in Drosophila, we found the spectraplakin Short stop (Shot), an actin/microtubule crosslinker. Loss of Shot causes microtubule orientation defects already during early dendrite development, when Shot is transiently recruited to tips of growing dendrites via its actin binding domain. Genetic and functional evidence suggest that Shots primary function in this process is to locally stabilize microtubules. We also provide evidence for a developmentally transient microtubule nucleation mechanism. Our data highlight the importance of transient and localized microtubule regulation for dendritic microtubule organization.

developmental biology↗

TORC1 regulation of dendrite regrowth after pruning is linked to actin and exocytosis

Neurite pruning and regrowth are important mechanisms to adapt neural circuits to distinct developmental stages. Neurite regrowth after pruning often depends on differential regulation of growth signaling pathways, but their precise mechanisms of action during regrowth are unclear. Here, we show that the PI3K/TORC1 pathway is required for dendrite regrowth after pruning in Drosophila peripheral neurons during metamorphosis. TORC1 impinges on translation initiation, and our analysis of 5 untranslated regions (UTRs) of remodeling factor mRNAs linked to actin suggests that TOR selectively stimulates the translation of regrowth over pruning factors. Furthermore, we find that dendrite regrowth also requires the GTPase RalA and the exocyst complex as regulators of polarised secretion, and we provide evidence that this pathway is also regulated by TOR. We propose that TORC1 coordinates dendrite regrowth after pruning by coordinately stimulating the translation of regrowth factors involved in cytoskeletal regulation and secretion. Author SummaryDuring development, neurons grow axons and dendrites that they use to make synaptic connections. Such connections are often fine-tuned through pruning and regrowth of axons and dendrites, but the coordination of the two processes is not well understood. It had previously been shown that hormone signaling suppresses the TORC1 growth pathway during pruning of Drosophila sensory neuron dendrites. We found that TORC1 is required for the subsequent regrowth of these dendrites. TORC1 activates protein biosynthesis, and our analyses suggest that it primarily targets neurite growth pathways, but not degenerative pathways. These growth pathways include the actin cytoskeleton and the secretion machinery with the small GTPase RalA. Thus, the TORC1 growth pathway is a major hub coordinating neurite pruning and regrowth.

developmental biology↗