The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning

PLoS Genetics, Journal Year: 2021, Volume and Issue: 17(7), P. e1009475 - e1009475

Published: July 1, 2021

The assembly of neuronal circuits involves the migrations neurons from their place birth to final location in nervous system, as well coordinated growth and patterning axons dendrites. In screens for genes required we identified catp-8/P5A-ATPase an important regulator neural patterning. P5A-ATPases are part P-type ATPases, a family proteins known serve conserved function transporters ions, lipids polyamines unicellular eukaryotes, plants, humans. While many ATPases is relatively understood, metazoans remained elusive. We show here, that Caenorhabditis elegans ortholog defined aspects system development. Specifically, serves functions shaping elaborately sculpted dendritic trees somatosensory PVD neurons. Moreover, axonal guidance repulsion at midline, embryonic postembryonic migrations. Interestingly, not all midline require catp-8/P5A-ATPase, although run same fascicles navigate space. Similarly, catp-8/P5A-ATPase. A CATP-8/P5A-ATPase reporter localized ER most, if all, tissues can both cell-autonomously non-autonomously regulate Genetic analyses establish multiple pathways, including Menorin pathway, previously shown control PVD, Wnt signaling, which Lastly, localizing select transmembrane necessary dendrite morphogenesis. Collectively, our studies suggest diverse, yet specific, roles different genetic pathways may be involved regulation or localization secreted specific subcellular compartments.

Language: Английский

---

Stochastic growth and selective stabilization generate stereotyped dendritic arbors

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 8, 2024

Stereotyped dendritic arbors are shaped by dynamic and stochastic growth during neuronal development. It remains unclear how guidance receptors ligands coordinate branch growth, retraction, stabilization to specify arbors. We previously showed that extracellular ligand SAX-7/LICAM dictates the shape of PVD sensory neuron via binding receptor DMA-1, a single transmembrane adhesion molecule. Here, we perform structure-function analyses DMA-1 unexpectedly find robust, does not require ligand-binding. Instead, ligand-binding inhibits prevents specifies arbor shape. Furthermore, demonstrate requires pool ligand-free which is maintained endocytosis reinsertion plasma membrane recycling endosomes. Mutants defective show severely truncated present model in mediates intrinsic, while instruct dendrite inhibiting growth.

Language: Английский

---

Sculpting the dendritic landscape: Actin, microtubules, and the art of arborization

Current Opinion in Cell Biology, Journal Year: 2023, Volume and Issue: 84, P. 102214 - 102214

Published: Aug. 4, 2023

Dendrites are intricately designed neuronal compartments that play a vital role in the gathering and processing of sensory or synaptic inputs. Their diverse elaborate structures distinct features organization function. Central to generation these dendritic arbors is cytoskeleton. In this review, we delve into current progress toward our understanding how dendrite generated maintained, focusing on actin microtubule

Language: Английский

---

Convertase-dependent regulation of membrane-tethered and secreted ligands tunes dendrite adhesion

Development, Journal Year: 2023, Volume and Issue: 150(18)

Published: Aug. 10, 2023

During neural development, cellular adhesion is crucial for interactions among and between neurons surrounding tissues. This function mediated by conserved cell molecules, which are tightly regulated to allow coordinated neuronal outgrowth. Here, we show that the proprotein convertase KPC-1 (homolog of mammalian furin) regulates Menorin complex during development PVD dendritic arbors in Caenorhabditis elegans. We found a finely antagonistic balance PVD-expressed epidermally expressed putative molecule MNR-1 (Menorin). Genetically, partial loss mnr-1 suppressed kpc-1, both kpc-1 transgenic overexpression resulted indistinguishable phenotypes dendrites. cell-surface localization DMA-1 leucine-rich transmembrane receptor neurons. Lastly, mutants showed increased amounts decreased muscle-derived LECT-2 (Chondromodulin II), also part complex. These observations suggest directly or indirectly controls abundance proteins from adjacent tissues, thereby providing negative feedback dendrite instructive cues

Language: Английский

---

Dendrite enlightenment

Current Opinion in Neurobiology, Journal Year: 2021, Volume and Issue: 69, P. 222 - 230

Published: June 13, 2021

Neuronal dendrites acquire complex morphologies during development. These are not just the product of cell-intrinsic developmental programs; rather they defined in close interaction with cellular environment. Thus, to understand molecular cascades that yield appropriate morphologies, it is essential investigate them vivo, actual tissue environment encountered by differentiating neuron developing animal. Particularly, genetic approaches have pointed factors controlling dendrite differentiation vivo. suggest localized and transient might underlie formation stabilization branches type–specific characteristics. Here, I highlight need for studies neuronal animal, challenges provided such an approach, promising pathways recently opened.

Language: Английский

---

Specific N‐glycans regulate an extracellular adhesion complex during somatosensory dendrite patterning

EMBO Reports, Journal Year: 2022, Volume and Issue: 23(7)

Published: May 19, 2022

Language: Английский

---

Potential Biomarkers for Parkinson Disease from Functional Enrichment and Bioinformatic Analysis of Global Gene Expression Patterns of Blood and Substantia Nigra Tissues

Bioinformatics and Biology Insights, Journal Year: 2023, Volume and Issue: 17

Published: Jan. 1, 2023

The Parkinson disease (PD) is the second most common neurodegenerative disorder affecting central nervous system and motor functions. biological complexity of PD yet to reveal potential targets for intervention or slow severity. Therefore, this study aimed compare fidelity blood substantia nigra (SN) tissue gene expression from patients provide a systematic approach predict role key genes pathobiology. Differentially expressed (DEGs) multiple microarray data sets SN GEO database are identified. Using theoretical network variety bioinformatic tools, we prioritized DEGs. A total 540 1024 DEGs were identified in samples, respectively. Functional pathways closely related such as ERK1 ERK2 cascades, mitogen-activated protein kinase (MAPK) signaling, Wnt, nuclear factor-κB (NF-κB), PI3K-Akt signaling observed by enrichment analysis. Expression patterns 13 similar both tissues. Comprehensive topological analysis regulatory networks additional 10 functionally connected with molecular mechanisms through mammalian target rapamycin (mTOR), autophagy, AMP-activated (AMPK) pathways. Potential drug molecules chemical-protein prediction These candidates can be further validated vitro/in vivo used biomarkers and/or novel pathology arrest delay neurodegeneration over years,

Language: Английский

---

Drosophila Dendritic Arborisation Neurons: Fantastic Actin Dynamics and Where to Find Them

Cells, Journal Year: 2021, Volume and Issue: 10(10), P. 2777 - 2777

Published: Oct. 16, 2021

Neuronal dendrites receive, integrate, and process numerous inputs therefore serve as the neuron's "antennae". Dendrites display extreme morphological diversity across different neuronal classes to match specific functional requirements. Understanding how this structural is specified important for shedding light on information processing in healthy diseased nervous system. Popular models vivo studies of dendrite differentiation are four dendritic arborization (c1da-c4da) neurons Drosophila larvae with their class-specific morphologies. Using da neurons, a combination live-cell imaging computational approaches have delivered distinct phases time course development from embryonic stages fully developed tree. With these data, we can start approaching basic logic behind differential development. A major role definition neuron-type morphologies played by dynamic actin-rich processes regulation properties. This review presents differences growth programs leading morphologically trees, focus key actin modulatory proteins. In addition, summarize requirements technological progress towards visualization manipulation such regulators vivo.

Language: Английский

---

Local Microtubule and F-Actin Distributions Fully Constrain the Spatial Geometry of Drosophila Sensory Dendritic Arbors

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6741 - 6741

Published: April 4, 2023

Dendritic morphology underlies the source and processing of neuronal signal inputs. Morphology can be broadly described by two types geometric characteristics. The first is dendrogram topology, defined length frequency arbor branches; second spatial embedding, mainly determined branch angles straightness. We have previously demonstrated that microtubules actin filaments are associated with elongation branching, fully constraining topology. Here, we relate local distribution these primary cytoskeletal components dendritic embedding. reconstruct analyze 167 sensory neurons from Drosophila larva encompassing multiple cell classes genotypes. observe branches a higher microtubule concentration tend to deviate less direction their parent across all neuron types. Higher also overall straighter. F-actin displays similar effect on angular deviation straightness, but not as consistently microtubule. These observations raise question whether associations between distributions geometry sufficient constraints reproduce type-specific architecture. Therefore, create computational model purely constrained composition measured real neurons. quantitatively captures both embedding topology tested groups. results suggest common developmental mechanism regulating diverse morphologies, where specify emergent arbors.

Language: Английский

---

The Zinc-BED transcription factor Bedwarfed promotes proportional dendritic growth and branching through transcriptional and translational regulation inDrosophila

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 15, 2023

Abstract Dendrites are the primary points of sensory or synaptic inputs to a neuron and play an essential role in integration neural function. Despite functional importance dendrites, relatively less is known about underlying mechanisms regulating cell-type specific dendritic patterning. Herein, we have dissected roles previously uncharacterized gene, CG3995 , development Drosophila melanogaster . which named bedwarfed ( bdwf ), encodes zinc-finger BED-type protein required for proportional growth branching arbors, exhibits nucleocytoplasmic expression, functions both transcriptional translational cellular pathways. At level, demonstrate reciprocal regulatory relationship between Bdwf homeodomain transcription factor (TF) Cut. We show that Cut positively regulates expression acts as downstream effector Cut-mediated development, whereas overexpression negatively multidendritic neurons. Proteomic analyses revealed interacts with ribosomal proteins disruption these produced phenotypically similar hypotrophy defects observed mutant further its interactors normal microtubule F-actin cytoskeletal architecture. Finally, our findings reveal promote translation ribosome trafficking along arbor. Taken together, results provide new insights into complex, combinatorial multi-functional factors (TFs) directing diversification development.

Language: Английский

---