ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Steering neuronal growth cones by shifting the imbalance between exocytosis and endocytosis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 47 citations in OpenAlex.
- From blueprint to build: Metal ions in peripheral nerve development and engineering regeneration.Bioactive materials · 2026Review
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- TOM-1/tomosyn acts with the UNC-6/netrin receptor UNC-5 to inhibit growth cone protrusion in Caenorhabditis elegans.Development (Cambridge, England) · 2023Article
- From whole organism to ultrastructure: progress in axonal imaging for decoding circuit development.Development (Cambridge, England) · 2021Review
- Inositol 1,4,5-Trisphosphate Receptor Type 3 Regulates Neuronal Growth Cone Sensitivity to Guidance Signals.iScience · 2020Article
- News about non-secretory exocytosis: mechanisms, properties, and functions.Journal of molecular cell biology · 2019Review
- Nestin in immature embryonic neurons affects axon growth cone morphology and Semaphorin3a sensitivity.Molecular biology of the cell · 2019Article
- Syntaxin-1/TI-VAMP SNAREs interact with Trk receptors and are required for neurotrophin-dependent outgrowth.Oncotarget · 2018Article
- Primary Cilia Reconsidered in the Context of Ciliopathies: Extraciliary and Ciliary Functions of Cilia Proteins Converge on a Polarity theme?BioEssays : news and reviews in molecular, cellular and developmental biology · 2018Review
- A conserved role for Syntaxin-1 in pre- and post-commissural midline axonal guidance in fly, chick, and mouse.PLoS genetics · 2018Article
- Molecular Analysis of Sensory Axon Branching Unraveled a cGMP-Dependent Signaling Cascade.International journal of molecular sciences · 2018Review
- Spatiotemporal organization of exocytosis emerges during neuronal shape change.The Journal of cell biology · 2018Article
- SNARE complex in axonal guidance and neuroregeneration.Neural regeneration research · 2018Review
- Revisiting Netrin-1: One Who Guides (Axons).Frontiers in cellular neuroscience · 2018Review
- S-palmitoylation Is Required for the Control of Growth Cone Morphology of DRG Neurons by CNP-Induced cGMP Signaling.Frontiers in molecular neuroscience · 2018Article
- Using the shared genetics of dystonia and ataxia to unravel their pathogenesis.Neuroscience and biobehavioral reviews · 2017Review
- Where does axon guidance lead us?F1000Research · 2017Review
- Beyond the cytoskeleton: The emerging role of organelles and membrane remodeling in the regulation of axon collateral branches.Developmental neurobiology · 2016Review
- Cyclic Nucleotide Control of Microtubule Dynamics for Axon Guidance.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extracellular molecular cues guide migrating growth cones along specific routes during development of axon tracts. Such processes rely on asymmetric elevation of cytosolic Ca(2+) concentrations across the growth cone that mediates its attractive or repulsive turning toward or away from the side with Ca(2+) elevation, respectively. Downstream of these Ca(2+) signals, localized activation of membrane trafficking steers the growth cone bidirectionally, with endocytosis driving repulsion and exocytosis causing attraction. However, it remains unclear how Ca(2+) can differentially regulate these opposite membrane-trafficking events. Here, we show that growth cone turning depends on localized imbalance between exocytosis and endocytosis and identify Ca(2+)-dependent signaling pathways mediating such imbalance. In embryonic chicken dorsal root ganglion neurons, repulsive Ca(2+) signals promote clathrin-mediated endocytosis through a 90 kDa splice variant of phosphatidylinositol-4-phosphate 5-kinase type-1γ (PIPKIγ90). In contrast, attractive Ca(2+) signals facilitate exocytosis but suppress endocytosis via Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and cyclin-dependent kinase 5 (Cdk5) that can inactivate PIPKIγ90. Blocking CaMKII or Cdk5 leads to balanced activation of both exocytosis and endocytosis that causes straight growth cone migration even in the presence of guidance signals, whereas experimentally perturbing the balance restores the growth cone's turning response. Remarkably, the direction of this resumed turning depends on relative activities of exocytosis and endocytosis, but not on the type of guidance signals. Our results suggest that navigating growth cones can be redirected by shifting the imbalance between exocytosis and endocytosis, highlighting the importance of membrane-trafficking imbalance for axon guidance and, possibly, for polarized cell migration in general.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.