ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
BDNF-mediated cerebellar granule cell development is impaired in mice null for CaMKK2 or CaMKIV.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 97 citations in OpenAlex.
- Effect ofIBRO neuroscience reports · 2025Article
- Ezh2 Delays Activation of Differentiation Genes During Normal Cerebellar Granule Neuron Development and in Medulloblastoma.bioRxiv : the preprint server for biology · 2024Article
- Loss of calcium/calmodulin-dependent protein kinase kinase 2, transferrin, and transferrin receptor proteins in the temporal cortex of Alzheimer's patients postmortem is associated with abnormal iron homeostasis: implications for patient survival.Frontiers in cell and developmental biology · 2024Article
- CaMKK2 as an emerging treatment target for bipolar disorder.Molecular psychiatry · 2023Review
- Fibroblast exosomal TFAP2C induced by chitosan oligosaccharides promotes peripheral axon regeneration via the miR-132-5p/CAMKK1 axis.Bioactive materials · 2023Article
- Expression in skin biopsies supports genetic evidence linking CAMKK2, P2X7R and P2X4R with HIV-associated sensory neuropathy.Journal of neurovirology · 2023Article
- Building better brains: the pleiotropic function of neurotrophic factors in postnatal cerebellar development.Frontiers in molecular neuroscience · 2023Review
- Neuronal CaMKK2 promotes immunosuppression and checkpoint blockade resistance in glioblastoma.Nature communications · 2022Article
- CaMKIV/CREB/BDNF signaling pathway expression in prefrontal cortex, amygdala, hippocampus and hypothalamus in streptozotocin-induced diabetic mice with anxious-like behavior.Experimental brain research · 2022Article
- Utilizing In Vivo Postnatal Electroporation to Study Cerebellar Granule Neuron Morphology and Synapse Development.Journal of visualized experiments : JoVE · 2021Article
- A complete map of the Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) signaling pathway.Journal of cell communication and signaling · 2021Article
- Combined Neuroprotective Strategies Blocked Neurodegeneration and Improved Brain Function in Senescence-Accelerated Mice.Frontiers in aging neuroscience · 2021Article
- The Role of Calmodulin in Tumor Cell Migration, Invasiveness, and Metastasis.International journal of molecular sciences · 2020Review
- Polymorphisms in CAMKK2 associate with susceptibility to sensory neuropathy in HIV patients treated without stavudine.Journal of neurovirology · 2019Article
- MARVELD1 depletion leads to dysfunction of motor and cognition via regulating glia-dependent neuronal migration during brain development.Cell death & disease · 2018Article
- Moving into shape: cell migration during the development and histogenesis of the cerebellum.Histochemistry and cell biology · 2018Review
- Inhibition of CaMKK2 Enhances Fracture Healing by Stimulating Indian Hedgehog Signaling and Accelerating Endochondral Ossification.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2018Article
- Using biomaterials to modulate chemotactic signaling for central nervous system repair.Biomedical materials (Bristol, England) · 2018Review
- BDNF activates an NFI-dependent neurodevelopmental timing program by sequestering NFATc4.Molecular biology of the cell · 2018Article
- Antidepression action of BDNF requires and is mimicked by Gαi1/3 expression in the hippocampus.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The Ca(2+)/calmodulin-activated kinases CaMKK2 and CaMKIV are highly expressed in the brain where they play important roles in activating intracellular responses to elevated Ca(2+). To address the biological functions of Ca(2+) signaling via these kinases during brain development, we have examined cerebellar development in mice null for CaMKK2 or CaMKIV. Here, we demonstrate that CaMKK2/CaMKIV-dependent phosphorylation of cAMP response element-binding protein (CREB) correlates with Bdnf transcription, which is required for normal development of cerebellar granule cell neurons. We show in vivo and in vitro that the absence of either CaMKK2 or CaMKIV disrupts the ability of developing cerebellar granule cells in the external granule cell layer to cease proliferation and begin migration to the internal granule cell layer. Furthermore, loss of CaMKK2 or CaMKIV results in decreased CREB phosphorylation (pCREB), Bdnf exon I and IV-containing mRNAs, and brain-derived neurotrophic factor (BDNF) protein in cerebellar granule cell neurons. Reexpression of CaMKK2 or CaMKIV in granule cells that lack CaMKK2 or CaMKIV, respectively, restores pCREB and BDNF to wild-type levels and addition of BDNF rescues granule cell migration in vitro. These results reveal a previously undefined role for a CaMKK2/CaMKIV cascade involved in cerebellar granule cell development and show specifically that Ca(2+)-dependent regulation of BDNF through CaMKK2/CaMKIV is required for this process.
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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.