Spinophilin modulates pain through suppressing dendritic spine morphogenesis via negative control of Rac1-ERK signaling in rat spinal dorsal horn

Wang, Jianglin; Wang, Yan; Sun, Wei; Yu, Yang; Wei, Na; Du, Rui; Yang, Yan; Liang, Ting; Wang, Xiaoliang; Ou, Cehua

doi:10.1016/j.nbd.2021.105302

Cited by 4 publications

(2 citation statements)

References 65 publications

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“…NEB2 is a regulatory subunit of protein phosphatase 1 [43] that controls serine/threonine dephosphorylation of several membrane proteins such as ion channels and certain G-protein coupled receptors [44] and is enriched in postsynaptic compartments [45] where it is involved in modulating spine maturation and morphology. [46] In accordance with this latter observation, the association of Kv1 with PP2BB is also lost in Lgi1 -/samples. PP2BB is a regulatory subunit of the activity-dependent serine/threonine-protein phosphatase calcineurin and plays an essential role in intracellular Ca 2+ -mediated signal transduction.…”

Section: Lost Kv 1 Partners In Lgi1supporting

confidence: 68%

Molecular Basis of Kv1 Channel Downregulation and Its Epileptogenic Implications in Lgi1 Knock-out Mice

Ramírez‐Franco

Debreux

Sangiardi

et al. 2023

Preprint

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The Kv1 members (KCNA, Shaker) of the voltage-gated potassium channels are implicated in determining key functional neuronal properties from spike generation at axonal initial segments to the control of synaptic strength at nerve terminals. In animal models of LGI1-dependent autosomal dominant lateral temporal lobe epilepsy (ADTLE), Kv1 channels are downregulated, suggesting their crucial involvement in epileptogenesis. The molecular basis of Kv1 channel-downregulation in LGI1 knock-out mice has not been elucidated and how the absence of this extracellular protein induces an important modification in the expression of Kv1 remains unknown. In this study we analyse by immunofluorescence the detailed modifications in neuronal Kv1.1 and Kv1.2 distribution throughout the hippocampal formation of LGI1 knock-out mice. We show that Kv1 downregulation is not restricted to the axonal compartment, but also takes place in the somatodendritic region and is accompanied by a drastic decrease in Kv2 expression levels. Moreover, we find that the downregulation of these Kv channels is associated with an important increase in bursting patterns. Finally, mass spectrometry uncovered key important modifications in the Kv1 interactome that highlight the epileptogenic implication of Kv1 downregulation in LGI1 knock-out animals.

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Section: Lost Kv 1 Partners In Lgi1supporting

confidence: 68%

Molecular Basis of Kv1 Channel Downregulation and Its Epileptogenic Implications in Lgi1 Knock-out Mice

Ramírez‐Franco

Debreux

Sangiardi

et al. 2023

Preprint

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“…20 Previous studies have reported that Rac1 signaling plays a crucial role in the initiation and development of acute and chronic pain from burns, neuropathy, etc. [21][22][23][24] Neuropathic pain can lead to some degree of dendritic spine remodeling and promote the increase of neuronal activity in WDR neurons in the deep lamellar layer of the dorsal horn of the spinal. 25,26 The enhancement of neuronal synaptic plasticity is the basis of central sensitization in neuropathic pain.…”

Section: Introductionmentioning

confidence: 99%

Rac1/PAK1 signaling contributes to bone cancer pain by Regulation dendritic spine remodeling in rats

Yang

et al. 2023

Mol Pain

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Bone cancer pain (BCP) is severe chronic pain caused by tumor metastasis to the bones, often resulting in significant skeletal remodeling and fractures. Currently, there is no curative treatment. Therefore, insight into the underlying mechanisms could guide the development of mechanism-based therapeutic strategies for BCP. We speculated that Rac1/PAK1 signaling plays a critical role in the development of BCP. Tumor cells implantation (TCI) into the tibial cavity resulted in bone cancer-associated mechanical allodynia. Golgi staining revealed changes in the excitatory synaptic structure of WDR (Wide-dynamic range) neurons in the spinal cord, including increased postsynaptic density (PSD) length and thickness, and width of the cleft. Behavioral and western blotting test revealed that the development and persistence of pain correlated with Rac1/PAK1 signaling activation in primary sensory neurons. Intrathecal injection of NSC23766, a Rac1 inhibitor, reduced the persistence of BCP as well as reversed the remodeling of dendrites. Therefore, we concluded that activation of the Rac1/PAK1 signaling pathway in the spinal cord plays an important role in the development of BCP through remodeling of dendritic spines. Modulation of the Rac1/PAK1 pathway may be a potential strategy for BCP treatment.

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Transcriptomic Profile Identifies Hippocampal Sgk1 as the Key Mediator of Ovarian Estrogenic Regulation on Spatial Learning and Memory and Aβ Accumulation

et al. 2022

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Spinophilin modulates pain through suppressing dendritic spine morphogenesis via negative control of Rac1-ERK signaling in rat spinal dorsal horn

Cited by 4 publications

References 65 publications

Molecular Basis of Kv1 Channel Downregulation and Its Epileptogenic Implications in Lgi1 Knock-out Mice

Molecular Basis of Kv1 Channel Downregulation and Its Epileptogenic Implications in Lgi1 Knock-out Mice

Rac1/PAK1 signaling contributes to bone cancer pain by Regulation dendritic spine remodeling in rats

Transcriptomic Profile Identifies Hippocampal Sgk1 as the Key Mediator of Ovarian Estrogenic Regulation on Spatial Learning and Memory and Aβ Accumulation

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