Autophagy-dependent filopodial kinetics restrict synaptic partner choice during Drosophila brain wiring

Kiral, Ferdi Rıdvan; Linneweber, Gerit Arne; Mathejczyk, Thomas F.; Georgiev, Svilen Veselinov; Wernet, Mathias F.; Hassan, Bassem A.; Kleist, Max von; Hiesinger, P. Robin

doi:10.1038/s41467-020-14781-4

Cited by 36 publications

(46 citation statements)

References 64 publications

(115 reference statements)

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“…G. Haydon et al, 1987). Furthermore, there is evidence in both vertebrate and invertebrate sensory circuits that direction and speed of axon-dendritic interactions can contribute to connection specificity (Balaskas et al, 2019;Kiral et al, 2020). Our study in the Drosophila neural superposition demonstrates how cell-autonomous control of velocity is instrumental in the precise wiring of a complex sensory circuit.…”

Section: Discussionmentioning

confidence: 69%

On the role of photoreceptor identity in controlling accurate wiring of theDrosophilavisual circuit

Altschuler

Wu³

2020

Preprint

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During development, neurons extend in search of synaptic partners. Precise control of axon extension velocity can therefore be crucial to ensuring proper circuit formation. How velocity is regulated - particularly by the extending axons themselves - remains poorly understood. Here, we investigate this question in the Drosophila visual system, where photoreceptors make precise connections with a specific set of synaptic partners that together create a circuit underpinning neural superposition (NSP). We used a combination of genetic perturbations and quantitative image analysis to investigate the influence of cell identity on growth cone velocity and subsequent spatial-temporal coincidence of presynaptic and postsynaptic neurons. Our study provides a case study of how cell autonomous properties of presynaptic axons play a pivotal role in controlling the dynamics of growing axons and determining the formation of a precise neuronal circuit.

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Section: Discussionmentioning

confidence: 69%

On the role of photoreceptor identity in controlling accurate wiring of theDrosophilavisual circuit

Altschuler

Wu³

2020

Preprint

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“…[38] In support of this idea, our group has recently reported a surprisingly prevalent ability of these R7 photoreceptors to form synapses with incorrect partners. [92] Drosophila R7 photoreceptor terminals are amongst the first neurons whose live dynamics have been recorded throughout the synapse formation process in intact brains. [93,94] Loss of autophagic degradation in the R7 cell leads to increased stability of synaptogenic filopodia.…”

Section: Permissive Functions Of Molecular Identification Tags Contrimentioning

confidence: 99%

“…[ 38 ] In support of this idea, our group has recently reported a surprisingly prevalent ability of these R7 photoreceptors to form synapses with incorrect partners. [ 92 ]…”

Section: Instructions Are Composites In Timementioning

confidence: 99%

“…[ 93,94 ] Loss of autophagic degradation in the R7 cell leads to increased stability of synaptogenic filopodia. [ 92 ] A consequence of this increase in filopodial stability is the formation of synapses with at least six incorrect postsynaptic partner neurons; these are neurons that should not form any synapses with R7 based on electron microscopy‐based connectome analysis. [ 95 ] Both autophagy and filopodial dynamics are generally considered permissive mechanisms.…”

Section: Instructions Are Composites In Timementioning

confidence: 99%

“…This results is an effective exclusion of many postsynaptic partners through fast filopodial kinetics. [ 92 ] In the absence of this kinetic restriction, several incorrect partner neurons are revealed as competent synaptic partners that are not prevent from synapse formation by any other mechanism. Kinetic restriction makes sense as a part of a composite instruction only as a contributing component in addition to other factors and conditions.…”

Section: Instructions Are Composites In Timementioning

confidence: 99%

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Brain wiring with composite instructions

Hiesinger

2020

BioEssays

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The quest for molecular mechanisms that guide axons or specify synaptic contacts has largely focused on molecules that intuitively relate to the idea of an "instruction." By contrast, "permissive" factors are traditionally considered background machinery without contribution to the information content of a molecularly executed instruction. In this essay, I recast this dichotomy as a continuum from permissive to instructive actions of single factors that provide relative contributions to a necessarily collaborative effort. Individual molecules or other factors do not constitute absolute instructions by themselves; they provide necessary context for each other, thereby creating a composite that defines the overall instruction. The idea of composite instructions leads to two main conclusions: first, a composite of many seemingly permissive factors can define a specific instruction even in the absence of a single dominant contributor; second, individual factors are not necessarily related intuitively to the overall instruction or phenotypic outcome.

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Autophagy and the endolysosomal system in presynaptic function

Andres-Alonso

Kreutz

Karpova

2020

Cell. Mol. Life Sci.

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The complex morphology of neurons, the specific requirements of synaptic neurotransmission and the accompanying metabolic demands create a unique challenge for proteostasis. The main machineries for neuronal protein synthesis and degradation are localized in the soma, while synaptic junctions are found at vast distances from the cell body. Sophisticated mechanisms must, therefore, ensure efficient delivery of newly synthesized proteins and removal of faulty proteins. These requirements are exacerbated at presynaptic sites, where the demands for protein turnover are especially high due to synaptic vesicle release and recycling that induces protein damage in an intricate molecular machinery, and where replacement of material is hampered by the extreme length of the axon. In this review, we will discuss the contribution of the two major pathways in place, autophagy and the endolysosomal system, to presynaptic protein turnover and presynaptic function. Although clearly different in their biogenesis, both pathways are characterized by cargo collection and transport into distinct membrane-bound organelles that eventually fuse with lysosomes for cargo degradation. We summarize the available evidence with regard to their degradative function, their regulation by presynaptic machinery and the cargo for each pathway. Finally, we will discuss the interplay of both pathways in neurons and very recent findings that suggest non-canonical functions of degradative organelles in synaptic signalling and plasticity.

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Autophagy-dependent filopodial kinetics restrict synaptic partner choice during Drosophila brain wiring

Cited by 36 publications

References 64 publications

On the role of photoreceptor identity in controlling accurate wiring of theDrosophilavisual circuit

On the role of photoreceptor identity in controlling accurate wiring of theDrosophilavisual circuit

Brain wiring with composite instructions

Autophagy and the endolysosomal system in presynaptic function

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