LIM domain only 4 protein promotes granulocyte colony-stimulating factor-induced signaling in neurons

Gomez-Smith, Mariana; Qin, Zhaohong; Zhou, Xun; Schock, Sarah C.; Chen, Hsiao‐Huei

doi:10.1007/s00018-009-0223-z

Cited by 17 publications

(13 citation statements)

References 43 publications

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“…Among other candidate genes that might interfere with the Satb2-mediated Ctip2 repression, we selected the transcriptional adaptor Lmo4. This factor interacts with several components of the NuRD complex, is highly expressed in the rostral F/M region, where C/S+ are more abundant, and only in scattered cells of the pS cortex at P0 ( Figure 4A ) ( Cederquist et al, 2013 ; Gomez-Smith et al, 2010 ; Huang et al, 2009 ; Singh et al, 2005 ). Lmo4 expression gradually increases in S1 at postnatal stages, reaching its peak in LL at P7, then in all layers at P21 ( Figure 4B ).…”

Section: Resultsmentioning

confidence: 99%

Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications

Harb

Magrinelli

Nicolas

et al. 2016

eLife

102

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During cortical development, the identity of major classes of long-distance projection neurons is established by the expression of molecular determinants, which become gradually restricted and mutually exclusive. However, the mechanisms by which projection neurons acquire their final properties during postnatal stages are still poorly understood. In this study, we show that the number of neurons co-expressing Ctip2 and Satb2, respectively involved in the early specification of subcerebral and callosal projection neurons, progressively increases after birth in the somatosensory cortex. Ctip2/Satb2 postnatal co-localization defines two distinct neuronal subclasses projecting either to the contralateral cortex or to the brainstem suggesting that Ctip2/Satb2 co-expression may refine their properties rather than determine their identity. Gain- and loss-of-function approaches reveal that the transcriptional adaptor Lmo4 drives this maturation program through modulation of epigenetic mechanisms in a time- and area-specific manner, thereby indicating that a previously unknown genetic program postnatally promotes the acquisition of final subtype-specific features.DOI: http://dx.doi.org/10.7554/eLife.09531.001

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Section: Resultsmentioning

confidence: 99%

Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications

Harb

Magrinelli

Nicolas

et al. 2016

eLife

102

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“…Building on these data, we found that chronic stress, through a glucocorticoid-dependent pathway, caused a reduction in palmitoylated LMO4 within the amygdala. Cell culture studies similarly showed that prolonged exposure to corticosterone to neuronal cells similarly caused a reduction in palmitoylation, and a subsequent translocation of LMO4 from the cytosol to the nucleus, where LMO4 functions as a transcription cofactor (Chen et al, 2002(Chen et al, , 2007a(Chen et al, , 2007bGomez-Smith et al, 2010;Schock et al, 2008) but no longer interacts with PTP1B. In line with this finding, PTP1B activity was elevated within the amygdala following chronic stress, and inhibition of PTP1B during chronic stress attenuated stress-induced suppression of eCB signaling within the amygdala and normalized changes in anxiety from chronic stress.…”

Section: Discussionmentioning

confidence: 99%

Chronic Stress Induces Anxiety via an Amygdalar Intracellular Cascade that Impairs Endocannabinoid Signaling

Qin

Zhou

Pandey

et al. 2015

Neuron

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Collapse of endocannabinoid (eCB) signaling in the amygdala contributes to stress-induced anxiety, but the mechanisms of this effect remain unclear. eCB production is tied to the function of the glutamate receptor mGluR5, itself dependent on tyrosine phosphorylation. Herein, we identify a novel pathway linking eCB regulation of anxiety through phosphorylation of mGluR5. Mice lacking LMO4, an endogenous inhibitor of the tyrosine phosphatase PTP1B, display reduced mGluR5 phosphorylation, eCB signaling, and profound anxiety that is reversed by genetic or pharmacological suppression of amygdalar PTP1B. Chronically stressed mice exhibited elevated plasma corticosterone, decreased LMO4 palmitoylation, elevated PTP1B activity, reduced amygdalar eCB levels, and anxiety behaviors that were restored by PTP1B inhibition or by glucocorticoid receptor antagonism. Consistently, corticosterone decreased palmitoylation of LMO4 and its inhibition of PTP1B in neuronal cells. Collectively, these data reveal a stress-responsive corticosterone-LMO4-PTP1B-mGluR5 cascade that impairs amygdalar eCB signaling and contributes to the development of anxiety.

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“…Appropriate empty vector or scrambled shRNA was used as a control. Cells were harvested 24 h after transfection, and RyR2 promoter-driven luciferase activity was normalized to ␤-galactosidase to control for transfection efficiency, as described previously (Chen et al, 2007b;Gomez-Smith et al, 2010).…”

Section: Methodsmentioning

confidence: 99%

“…Hippocampal protein extracts from 1-monthold mice were harvested and prepared for Western blot analysis as described previously (Chen et al, 2007b;Gomez-Smith et al, 2010). Primary mouse monoclonal antibodies to ryanodine receptor 2 (Affinity Bioreagents) (Stutzmann et al, 2006) and to GAPDH (Abcam) were used.…”

Section: Methodsmentioning

confidence: 99%

LIM Domain Only 4 (LMO4) Regulates Calcium-Induced Calcium Release and Synaptic Plasticity in the Hippocampus

Qin¹,

Zhou²,

Gomez-Smith³

et al. 2012

J. Neurosci.

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The LIM domain only 4 (LMO4) transcription cofactor activates gene expression in neurons and regulates key aspects of network formation, but the mechanisms are poorly understood. Here, we show that LMO4 positively regulates ryanodine receptor type 2 (RyR2) expression, thereby suggesting that LMO4 regulates calcium-induced calcium release (CICR) in central neurons. We found that CICR modulation of the afterhyperpolarization in CA3 neurons from mice carrying a forebrain-specific deletion of LMO4 (LMO4 KO) was severely compromised but could be restored by single-cell overexpression of LMO4. In line with these findings, two-photon calcium imaging experiments showed that the potentiation of RyR-mediated calcium release from internal stores by caffeine was absent in LMO4 KO neurons. The overall facilitatory effect of CICR on glutamate release induced during trains of action potentials was likewise defective in LMO4 KO, confirming that CICR machinery is severely compromised in these neurons. Moreover, the magnitude of CA3-CA1 longterm potentiation was reduced in LMO4 KO mice, a defect that appears to be secondary to an overall reduced glutamate release probability. These cellular phenotypes in LMO4 KO mice were accompanied with deficits in hippocampus-dependent spatial learning as determined by the Morris water maze test. Thus, our results establish LMO4 as a key regulator of CICR in central neurons, providing a mechanism for LMO4 to modulate a wide range of neuronal functions and behavior.

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LIM domain only 4 protein promotes granulocyte colony-stimulating factor-induced signaling in neurons

Cited by 17 publications

References 43 publications

Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications

Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications

Chronic Stress Induces Anxiety via an Amygdalar Intracellular Cascade that Impairs Endocannabinoid Signaling

LIM Domain Only 4 (LMO4) Regulates Calcium-Induced Calcium Release and Synaptic Plasticity in the Hippocampus

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