TRPM7 Regulates Axonal Outgrowth and Maturation of Primary Hippocampal Neurons

Turlova, Ekaterina; Bae, Christine You-jin; Deurloo, Marielle; Chen, Wenliang; Barszczyk, Andrew; Horgen, F. David; Fleig, Andrea; Feng, Zhong‐Ping; Sun, Hong‐Shuo

doi:10.1007/s12035-014-9032-y

Cited by 54 publications

(51 citation statements)

References 50 publications

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“…TRPM7 is known to inactivate LIMK1 which in turn is a suppressor of cofilin (Arber et al, 1998; Meng et al, 2003; Meng et al, 2002). Recently, inhibition and knockdown of TRPM7 was shown to increase the rate of progression through neuronal development stages and increase the length of axons (Turlova et al, 2016). Some of TPRM7’s effects could be through phosphorylation of Tmods, which are present in axonal shafts (Fath et al, 2011).…”

Section: Tropomodulins and Tropomyosins – Discovery Structure And Rmentioning

confidence: 99%

Actin regulation by tropomodulin and tropomyosin in neuronal morphogenesis and function

Gray

Kostyukova

Fath

2017

Molecular and Cellular Neuroscience

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Actin is a profoundly influential protein; it impacts, among other processes, membrane morphology, cellular motility, and vesicle transport. Actin can polymerize into long filaments that push on membranes and provide support for intracellular transport. Actin filaments have polar ends: the fast-growing (barbed) end and the slow-growing (pointed) end. Depolymerization from the pointed end supplies monomers for further polymerization at the barbed end. Tropomodulins (Tmods) cap pointed ends by binding onto actin and tropomyosins (Tpms). Tmods and Tpms have been shown to regulate many cellular processes; however, very few studies have investigated their joint role in the nervous system. Recent data directly indicate that they can modulate neuronal morphology. Additional studies suggest that Tmod and Tpm impact molecular processes influential in synaptic signaling. To facilitate future research regarding their joint role in actin regulation in the nervous system, we will comprehensively discuss Tpm and Tmod and their known functions within molecular systems that influence neuronal development.

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Section: Tropomodulins and Tropomyosins – Discovery Structure And Rmentioning

confidence: 99%

Actin regulation by tropomodulin and tropomyosin in neuronal morphogenesis and function

Gray

Kostyukova

Fath

2017

Molecular and Cellular Neuroscience

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“…Primary cortical cultures were prepared from E16 CD1 mice as previously described (24). Cells were plated on poly-D-lysine coated plates using Neurobasal culture medium at the desired density (1 3 10 5 per well) and maintained at 37°C in a humidified 5% CO 2 atmosphere.…”

Section: Primary Cortical Culturementioning

confidence: 99%

Cerebrovascular Safety of Sulfonylureas: The Role of KATP Channels in Neuroprotection and the Risk of Stroke in Patients With Type 2 Diabetes

Wang

et al. 2016

Diabetes

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Sulfonylureas are ATP-sensitive potassium (K ATP ) channel blockers commonly used in the treatment of type 2 diabetes mellitus (T2DM). Activation of K ATP channels plays a neuroprotective role in ischemia; thus, whether sulfonylureas affect the outcomes of stroke in patients with T2DM needs to be further studied. In our study, streptozotocin (STZ)-induced diabetic mice subjected to transient middle cerebral artery occlusion (MCAO) showed larger areas of brain damage and poorer behavioral outcomes. Blocking the K ATP channel by tolbutamide increased neuronal injury induced by oxygen-glucose deprivation (OGD) in vitro and permanent MCAO (pMCAO) in vivo. Activating the K ATP channel by diazoxide reduced the effects of both the OGD and pMCAO. Western blot analysis in STZ mouse brains indicated an early increase in protein levels of N-methyl-D-aspartate receptor 2B and postsynaptic density protein-95, followed by a decrease in phosphorylation of glycogen synthase kinase 3b. Our systematic meta-analysis indicated that patients with T2DM treated with sulfonylureas had a higher odds ratio for stroke morbidity than those who received comparator drugs. Taken together, these results suggest that sulfonylurea treatment in patients with T2DM may inhibit the neuroprotective effects of K ATP channels and increase the risk of stroke.

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“…The importance of neurite outgrowth during brain development cannot be overstated as disruptions to this process have been associated to Down syndrome (Becker et al, 1986) and Fragile X Syndrome (Dierssen and Ramakers, 2006). Interestingly, a recent study by Turlova et al, 2016 reported that TRPM7 negatively regulates neurite outgrowth in cultured hippocampal neurons. They demonstrated that neurite length was increased after performing targeted knockdown of TRPM7 with shRNA.…”

Section: Discussionmentioning

confidence: 99%

mRNA expression of transient receptor potential melastatin (TRPM) channels 2 and 7 in perinatal brain development

Ratnam¹,

Chan

Lesani³

et al. 2018

Intl J of Devlp Neuroscience

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TRPM7 and TRPM2 are non-specific cation channels of the Transient Receptor Potential channel superfamily. Each channel has gained attention for their potential to mediate oxidative and anoxic cell death (Rama and García, 2016; Nazıroğlu, 2011a; Abiria et al., 2017; Sun, 2017), however their physiological expression and roles in the developing brain remain poorly defined. We employed real-time reverse transcription PCR to examine mRNA expression of TRPM7 and TRPM2 in the developing rat brain and brain-specific cell types. We determined the temporal and spatial expression patterns at four developmental time points (postnatal day 7, 14, 21, and 90) in four critical regions of the brain (cortex, hippocampus, striatum, and cerebellum) and examined gene expression in neuronal, astrocytic, and microglial primary cell cultures. Our results revealed that TRPM7 mRNA expression peaks in the cortex at 2-weeks after birth, and thus correlates most closely with a period of rat brain development associated with neurite outgrowth, which is heightened at 2-weeks after birth. Our cell-specific gene expression assays revealed that TRPM7 was expressed at equivalent levels in neurons, astrocytes, and microglia. Conversely, TRPM2 was most highly expressed in microglia with little expression in neurons and astrocytes. In the hippocampus and striatum, the expression profile of TRPM2 parallels the perinatal expression timeline for microglial infiltration and maturation in the rat brain. Microglial maturation is highest from the time of birth, up to 7-days, but subsequently declines. The latter developmental expression profiles indicate a role for TRPM2 in microglial activation.

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TRPM7 Regulates Axonal Outgrowth and Maturation of Primary Hippocampal Neurons

Cited by 54 publications

References 50 publications

Actin regulation by tropomodulin and tropomyosin in neuronal morphogenesis and function

Actin regulation by tropomodulin and tropomyosin in neuronal morphogenesis and function

Cerebrovascular Safety of Sulfonylureas: The Role of KATP Channels in Neuroprotection and the Risk of Stroke in Patients With Type 2 Diabetes

mRNA expression of transient receptor potential melastatin (TRPM) channels 2 and 7 in perinatal brain development

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