Gamma synuclein: Subcellular localization in neuronal and non‐neuronal cells and effect on signal transduction

Surguchov, Andrei; Palazzo, Robert E.; Surgucheva, Irina

doi:10.1002/cm.1035

Cited by 58 publications

(61 citation statements)

References 44 publications

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“…4). γ-Synuclein (SNCG) regulates lipid metabolism in the brain (58) and plays a role in synaptic plasticity and formation (59,60) and neurofilament network integrity (61). Other genes have a lessobvious role in connectivity.…”

Section: And 7)mentioning

confidence: 99%

Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain

Krienen

Yeo

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

214

203

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The human brain is patterned with disproportionately large, distributed cerebral networks that connect multiple association zones in the frontal, temporal, and parietal lobes. The expansion of the cortical surface, along with the emergence of long-range connectivity networks, may be reflected in changes to the underlying molecular architecture. Using the Allen Institute's human brain transcriptional atlas, we demonstrate that genes particularly enriched in supragranular layers of the human cerebral cortex relative to mouse distinguish major cortical classes. The topography of transcriptional expression reflects large-scale brain network organization consistent with estimates from functional connectivity MRI and anatomical tracing in nonhuman primates. Microarray expression data for genes preferentially expressed in human upper layers (II/III), but enriched only in lower layers (V/VI) of mouse, were cross-correlated to identify molecular profiles across the cerebral cortex of postmortem human brains (n = 6). Unimodal sensory and motor zones have similar molecular profiles, despite being distributed across the cortical mantle. Sensory/motor profiles were anticorrelated with paralimbic and certain distributed association network profiles. Tests of alternative gene sets did not consistently distinguish sensory and motor regions from paralimbic and association regions: (i) genes enriched in supragranular layers in both humans and mice, (ii) genes cortically enriched in humans relative to nonhuman primates, (iii) genes related to connectivity in rodents, (iv) genes associated with human and mouse connectivity, and (v) 1,454 gene sets curated from known gene ontologies. Molecular innovations of upper cortical layers may be an important component in the evolution of long-range corticocortical projections.corticocortical connectivity | human transcriptome | association cortex | supragranular | brain evolution P atterns of gene expression in the cerebral cortex are generally conserved across species, reflecting strong constraints in the development and evolution of cortical architecture (1-6). Previous work examining transcriptional variation in nonhuman primates and rodents indicate that molecular similarities between cortical regions in the adult brain are best explained by spatial proximity (7, 8). Molecular variation often takes the form of graded expression along a principal axis, in many cases appearing as rostrocaudal gradients across the cortex (8). The strong tendency for transcriptional variation to follow spatial proximity in the adult cortex likely reflects both functional gradients, as well as their developmental origins in terms of physical and temporal adjacency during neurogenesis of cells destined for neighboring locations in the cortex (at least for cells derived from the ventricular proliferative pool) (7).Spatial proximity likely captures the major features governing how molecular profiles vary across the cortex in all species, including humans. However, the expansion of the cerebral cortex in primates...

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Section: And 7)mentioning

confidence: 99%

Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain

Krienen

Yeo

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

214

203

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“…Despite the mounting evidence that links BCSG1 with breast tumorigenesis, currently little is known about how BCSG1 exerts these oncogenic functions. Recently, an immunostaining study conducted by Surguchov et al, 2001 has shown that BCSG1 is localized to poles of spindle in mitotic cells and suggested that BCSG1 might be a centrosomal protein.…”

Section: Introductionmentioning

confidence: 99%

Breast cancer-specific gene 1 interacts with the mitotic checkpoint kinase BubR1

et al. 2003

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The abnormal expression of breast cancer-specific gene 1 (BCSG1) in malignant mammary epithelial cells is highly associated with the development and progression of breast cancer. A series of in vitro and in vivo studies performed in our laboratory and others have demonstrated that BCSG1 expression significantly stimulates proliferation, invasion, and metastasis of breast cancer cells. However, currently little is known about how BCSG1 exerts its oncogenic functions. To elucidate the cellular mechanisms underlying the effects of BCSG1 in breast cancer cells, we used a yeast two-hybrid system to screen for proteins that could associate with BCSG1. Through this screening, we identified the mitotic checkpoint protein BubR1 as a novel binding partner of BCSG1. The specific association of BCSG1 with BubR1 in breast cancer cells was demonstrated by immunoprecipitation and GST pull-down assays. Intriguingly, experiments conducted in four different cell lines all showed that exogenous expressions of BCSG1 consistently reduce the cellular levels of the BubR1 protein without affecting BubR1 mRNA expression. The tendency of endogenous BCSG1 expression coinciding with lower BubR1 protein levels was also observed in seven out of eight breast cancer cell lines. We further showed that the reducing effect of BCSG1 on BubR1 protein expression could be prevented by treating BCSG1-transfected cells with MG-132, a selective 26S proteasome inhibitor, implying that the proteasome machinery may be involved in the BCSG1-induced reduction of the BubR1 protein. Accompanied with a reduction of BubR1 protein level, BCSG1 expression resulted in multinucleation of breast cancer cells upon treatment with spindle inhibitor nocodazole, indicating an impaired mitotic checkpoint. Taken together, our novel findings suggest that BCSG1 may accelerate the progression of breast cancer at least in part by compromising the mitotic checkpoint control through inactivation of BubR1.

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“…The other members of the synuclein family are b-and g-synuclein (bSyn, g-Syn), whose function remains elusive . g-Syn is expressed in the central nervous system (Brenz Verca et al, 2003;Surguchov et al, 1999Surguchov et al, , 2001) and periphery. g-Syn is upregulated in some breast and prostate cancers, and cells expressing this protein have been found to be resistant to specific chemotherapeutic agents that disrupt the cytoskeleton (Gupta et al, 2003a, b;Ji et al, 1997;Pan et al, 2002;Wu et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Desipramine Modulation of α-, γ-Synuclein, and the Norepinephrine Transporter in an Animal Model of Depression

Jeannotte

McCarthy

Redei

et al. 2008

Neuropsychopharmacol

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The mechanisms underlying depression remain elusive. We previously determined that a-synuclein (a-Syn) modulates the activity and trafficking of the norepinephrine transporter (NET) in a manner that is dependent on its interactions with microtubules (MTs). Here we sought to determine if a-Syn, or the other synuclein family members, b-synuclein (b-Syn) and g-synuclein (g-Syn), modulate NET activity in an animal model of depression, the Wistar-Kyoto (WKY) rat. The NET-selective antidepressant desipramine (DMI) was chronically administered for 14 days to WKY rats and the strain from which it was outbred that does not show depressive-like behavior, the Wistar rat. This drug regimen induced significant behavioral improvements in the WKY, but not the Wistar rat, in the forced swim test. In WKY rats there was an overexpression of g-Syn which was reduced following DMI treatment. In parallel, DMI caused an increase in both a-Syn and NET in the frontal cortex. Frontal cortex synaptosomes from WKY rats were not sensitive to nocodazole, a compound that promotes MT destabilization. However, in WKYs treated with DMI, nocodazole induced an increase in [ 3 H]-NE uptake. This trend was reversed in Wistars. Underlying these DMI-induced changes were alterations in the protein interactions between the synucleins and NET with the tubulins. These results are the first to implicate a-Syn or g-Syn in the pathophysiology of depression and suggest that targeting synucleins may provide a new therapeutic option for depression.

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Gamma synuclein: Subcellular localization in neuronal and non‐neuronal cells and effect on signal transduction

Cited by 58 publications

References 44 publications

Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain

Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain

Breast cancer-specific gene 1 interacts with the mitotic checkpoint kinase BubR1

Desipramine Modulation of α-, γ-Synuclein, and the Norepinephrine Transporter in an Animal Model of Depression

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