Kinase Signaling in Dendritic Development and Disease

Nourbakhsh, Kimya; Yadav, Smita

doi:10.3389/fncel.2021.624648

Cited by 20 publications

(18 citation statements)

References 242 publications

(300 reference statements)

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“…In addition to these roles for CaMKII in Hebbian plasticity and learning, CaMKII is important for structural plasticity at dendritic spines. Here, CaMKII interacts with the dendritic cytoskeleton to drive spine enlargement 49 , 50 . Finally, CaMKII serves as a scaffold to promote the assembly of signaling machinery in dendrites 51 .…”

Section: Discussionmentioning

confidence: 99%

A glutamate receptor C-tail recruits CaMKII to suppress retrograde homeostatic signaling

et al. 2022

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Presynaptic homeostatic plasticity (PHP) adaptively enhances neurotransmitter release following diminished postsynaptic glutamate receptor (GluR) functionality to maintain synaptic strength. While much is known about PHP expression mechanisms, postsynaptic induction remains enigmatic. For over 20 years, diminished postsynaptic Ca2+ influx was hypothesized to reduce CaMKII activity and enable retrograde PHP signaling at the Drosophila neuromuscular junction. Here, we have interrogated inductive signaling and find that active CaMKII colocalizes with and requires the GluRIIA receptor subunit. Next, we generated Ca2+-impermeable GluRs to reveal that both CaMKII activity and PHP induction are Ca2+-insensitive. Rather, a GluRIIA C-tail domain is necessary and sufficient to recruit active CaMKII. Finally, chimeric receptors demonstrate that the GluRIIA tail constitutively occludes retrograde homeostatic signaling by stabilizing active CaMKII. Thus, the physical loss of the GluRIIA tail is sensed, rather than reduced Ca2+, to enable retrograde PHP signaling, highlighting a unique, Ca2+-independent control mechanism for CaMKII in gating homeostatic plasticity.

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Section: Discussionmentioning

confidence: 99%

A glutamate receptor C-tail recruits CaMKII to suppress retrograde homeostatic signaling

et al. 2022

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“…Synapse‐associated proteins, particularly synaptophysin and PSD‐95, are hallmarks of synaptic plasticity and play a vital part in memory (Nourbakhsh & Yadav, 2021). Studies have confirmed that the protein level of synaptophysin and PSD‐95 in 19‐month‐old mice were significantly down‐regulated compared with 3‐month‐old mice (Vazquez‐Roque et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Polygonatum sibiricum ameliorated cognitive impairment of naturally aging rats through BDNF–TrkB signaling pathway

Zhang

et al. 2022

Journal of Food Biochemistry

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Cognitive dysfunction is high in the elderly population and seriously affects the quality of life. Brain‐derived neurotrophic factor (BDNF) is one of the key neurotrophic proteins, and activation of BDNF–TrkB is considered an effective strategy to improve cognitive dysfunction during aging. In this study, administration of polygonatum sibiricum (PS) for 5 months effectively ameliorates the cognitive function, improving the Nissl body state in cortex and hippocampus in aging rats. In addition, PS can improve the synaptic structure and increase the number of synapses. Furthermore, PS reverses the reduction of synaptic plasticity‐related proteins postsynaptic density protein 95 (PSD‐95) and synaptophysin during aging and up‐regulates the expression of BDNF–TrkB. In conclusion, PS improves cognitive dysfunction and enhances synaptic plasticity in naturally aged rats by regulating the BDNF–TrkB signaling pathway. PS has the potential to be developed as a novel and promising functional health food for the elderly. Practical applications Polygonatum sibiricum (PS) is a traditional Chinese medicine, which has been included in the homologous plant of medicine and food. PS has been widely used to treat lung diseases, diabetes and antiaging in clinical. Studies have confirmed that PS can accelerate the repair and regeneration of damaged neurons, reverse the changes in synaptic structure, and improve the ability of learning and memory. Our study confirmed that PS significantly improved the cognitive function in aging rats. PS has great potential to be developed as a functional food for improving neurological function and anti‐aging.

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“…Even though the kinase domain is highly conserved, these three TAO kinases have divergent C-terminal tails that confer them with specific and distinct functions. Both TAOK1 and TAOK2 are associated with neurodevelopmental disorders (Nourbakhsh and Yadav, 2021). Recently, we identified TAOK2 as a transmembrane kinase that tethers the endoplasmic reticulum to microtubules (Nourbakhsh et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Neurodevelopmental disorder associated mutations in TAOK1 reveal its function as a plasma membrane remodeling kinase

Beeman

Sapre

Ong

et al. 2022

Preprint

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Mutations in TAOK1, a serine-threonine kinase encoding gene are strongly associated with both autism spectrum disorder (ASD) and neurodevelopmental delay (NDD). However, molecular function of this evolutionarily conserved kinase and the mechanisms through which TAOK1 mutations lead to neuropathology are unknown. Here, we showed that TAOK1 is highly expressed in neurons within the brain, and has a functional role in remodeling the plasma membrane through direct association with phosphoinositides. We characterized four NDD-associated TAOK1 mutations, and demonstrated that these mutations render TAOK1 catalytically dead. Kinase dead TAOK1 mutants were aberrantly trapped in membrane-bound state, which induced exuberant membrane protrusions. Expression of TAOK1 disease mutants in hippocampal neurons led to abnormal growth of the dendritic arbor. The coiled-coil region C-terminal to the kinase domain are predicted to fold into a triple helix. We showed that this triple helix directly bound phospholipids, and was required for both TAOK1 membrane association and induction of aberrant protrusions. Further, TAOK1 mutants were rescued from their membrane-trapped state by exogenous expression of the isolated kinase domain. Utilizing mass-spectrometry, we identified critical residues in the triple helix phosphorylated by TAOK1 that autoregulated its plasma membrane association. These findings define a previously unknown function of TAOK1 as a unique plasma membrane remodeling kinase, and reveal the underlying mechanisms through which TAOK1 dysfunction leads to neurodevelopmental disorders.

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Kinase Signaling in Dendritic Development and Disease

Cited by 20 publications

References 242 publications

A glutamate receptor C-tail recruits CaMKII to suppress retrograde homeostatic signaling

A glutamate receptor C-tail recruits CaMKII to suppress retrograde homeostatic signaling

Polygonatum sibiricum ameliorated cognitive impairment of naturally aging rats through BDNF–TrkB signaling pathway

Neurodevelopmental disorder associated mutations in TAOK1 reveal its function as a plasma membrane remodeling kinase

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