Biology subjects

Prevarskaya, N.

Publications and source records attributed to Prevarskaya, N..

3 recordsLinked to original sources

bioRxiv2024

TRPM8 channels control Golgi morphology through an AR-dependent induction of the Scd1 gene and modulation of unsaturated lipid content

Transient receptor potential melastatin 8 (TRPM8), the cold and menthol receptor is essential to thermosensation, although its roles in organs within the body are still unclear. Besides TRPM8, we previously cloned several isoforms, like 4TM-TRPM8, which can be expressed with or without TRPM8. In this study, we characterize the human TRPM8(85) in ER membranes in the vicinity of Golgi apparatus (GA) and mitochondria in prostate epithelial cells. Silencing of TRPM8(85) induces lipid droplet accumulation, GA expansion and fragmentation associated with a drop in the vesicular trafficking to plasmalemma. Furthermore, lipidomic analysis reveals a strong shift in unsaturated fatty acids (UFAs), induced by TRPM8(85) silencing and to a lesser extent silencing of TRPM8. UFAs increase is caused by the induction of {Delta}9 stearoyl desaturase (Scd1) gene. Silencing SCD1 or palmitate incubation prevent GA expansion in TRPM8(85)-silenced cells. Finally, we demonstrated that TRPM8 regulates SCD1 via the androgen receptor.

cell biology↗

bioRxiv2021

Rev-erb-α controls skeletal muscle calcium homeostasis through myoregulin repression: implications in Duchenne Muscular Dystrophy

The sarcoplasmic reticulum (SR) plays an important role in calcium homeostasis. SR calcium mishandling is described in pathological conditions such as myopathies. Here, we investigated whether the nuclear receptor Rev-erb- regulates skeletal muscle SR calcium homeostasis. Our data demonstrate that Rev-erb invalidation in mice impairs SERCA-dependent SR calcium uptake. Rev-erb- acts on calcium homeostasis by repressing the SERCA inhibitor Myoregulin, through direct binding to its promoter. Restoration of Myoregulin counteracts the effects of REV-ERB- overexpression on SR calcium content. Interestingly, myoblasts from Duchenne myopathy patients display downregulated REV-ERB expression, whereas pharmacological Rev-erb activation ameliorates SR calcium homeostasis, and improves muscle structure and function in dystrophic mdx/Utr+/- mice. Our findings demonstrate that Rev-erb- regulates muscle SR calcium homeostasis, pointing to its therapeutic interest for mitigating myopathy.

cell biology↗

bioRxiv2020

Malignant assignment of neuronal Na+ leak channel, NALCN: governor of Ca2+ oscillations-encoded invadopodogenesis

Cytosolic Ca2+ oscillations provide signaling input to several effector systems of the cell. These include neuronal development, migration and networking. Although similar signaling events are hijacked by highly aggressive cancer cells, the complexity of the neuron-like remodeling in metastasis remains to be explored. Here, using a variety of in vitro and in vivo techniques we show that strongly metastatic prostate cancer cells acquire specific Na+/Ca2+ signature required for persistent invasion. We identify the neuronal Na+ leak channel, NALCN, at the hot spots of the Ca2+ wave initiation and invadopodia formation. Mechanistically, NALCN associates functionally with plasmalemmal and mitochondrial Na+/Ca2+ exchangers, reactive oxygen species and store-operated channels to generate intracellular Ca2+ oscillations. In turn, this stimulates the activity of protooncogene Src kinase co-localized with NALCN, actin remodeling and secretion of proteolytic enzymes, thus increasing an invasive potential of the cancer cells and metastatic lesions in vivo (accessed in pre-clinical models). Overall, our findings provide new insight into the signaling pathway specific for metastatic cells where NALCN plays the role of the persistent invasion "launcher and controller".

cell biology↗