Biology subjects

Cong, R.

Publications and source records attributed to Cong, R..

3 recordsLinked to original sources

bioRxiv2024

α/β-Hydrolase domain-containing 6 (ABHD6) accelerates the desensitization and deactivation of TARP γ-2-containing AMPA receptors

AMPA receptors (AMPARs) mediate most of the fast excitatory synaptic transmission in the mammalian brain. Their efficacy in responding to presynaptic glutamate release depends on their kinetics, which are determined by AMPARs and their auxiliary subunit composition. /{beta}-Hydrolase domain-containing 6 (ABHD6) is an AMPAR auxiliary subunit that has been shown to negatively regulate the surface delivery of AMPARs and AMPAR-mediated currents. Overexpression of ABHD6 has been shown to decrease the rising slope and increase the decay {tau} of mEPSCs. However, whether ABHD6 is involved in regulating AMPAR kinetics remains unclear. Here, we found that ABHD6 itself had no effect on the gating kinetics of GluA1 and GluA2(Q) containing homomeric receptors. However, in the presence of the auxiliary subunit TARP {gamma}-2, ABHD6 accelerated the deactivation and desensitization of both GluA1 and GluA2(Q) containing homomeric receptors independent of their splicing isoforms (flip and flop) and the editing isoforms of GluA2 (R or G at position 764), except for the deactivation of GluA2(Q)i-G isoform. Besides, the recovery from desensitization of GluA1 with flip splicing isoform was slowed by the co-expression of ABHD6 in the presence of TARP {gamma}-2. Furthermore, ABHD6 accelerated the deactivation and desensitization of GluA1i/GluA2(R)i-G and GluA2(R)i-G/GluA3(R)i heteromeric receptors in the presence of TARP {gamma}-2. We also found that ABHD6-knockout neurons displayed slower deactivation and desensitization. Therefore, these results demonstrate that ABHD6 regulates AMPAR gating kinetics in a TARP {gamma}-2-dependent manner. SIGNIFICANCE STATEMENTThe efficacy of AMPARs in responding to presynaptic glutamate release depends on their kinetics, including deactivation, desensitization, and recovery from desensitization, which are determined by AMPARs and their auxiliary subunit composition. Using ultra-fast application of glutamate and outside-out patch recordings, we found that, in the presence of the auxiliary subunit TARP {gamma}-2, ABHD6 accelerated the deactivation and desensitization of GluA1i/GluA2(R)i-G and GluA2(R)i-G/GluA3(R)i heteromeric receptors and GluA1 and GluA2(Q) containing homomeric receptors independent of their splicing isoforms (flip and flop) and the editing isoforms of GluA2 (R or G at position 764), except for the deactivation of GluA2(Q)i-G isoform. In ABHD6 knockout neurons, we also observed slower deactivation and desensitization. These results demonstrated that ABHD6 regulates AMPAR gating kinetics in a TARP {gamma}-2-dependent manner.

neuroscience↗

bioRxiv2024

Novel Ser74 of NF-kappaB/CgIkappaBalpha Phosphorylated by MAPK/ERK Regulates Temperature Adaptation in Oysters

Phosphorylation of I{kappa}B at Ser32 and Ser36 by IKKs during biotic stress triggers its ubiquitin-proteasome degradation, causing to the nuclear translocation of REL, representing a key cascade mechanism in metazoans conserved and immune core signaling pathway, NF-{kappa}B. However, studies on its response to abiotic stress and signal transduction by phosphorylation in mollusks are lacking. Here, we firstly report a novel heat-induced phosphorylation site (Ser74) at the major NF-{kappa}B/CgI{kappa}B of oysters, phosphorylated by MAPK/CgERK1/2, which independently mediated the subsequent ubiquitin-proteasome degradation without phosphorylation at Ser32 and Ser36 and decreased thermal stability. The degradation of CgI{kappa}B promoted CgREL nuclear translocation, which stimulated cell survival related gene expression to defend against thermal stress. The MAPK and NF-{kappa}B pathways exhibited stronger activation patterns in higher environmental temperature and in the warm-adapted Crassostrea angulata than those in the cold-adapted C. gigas-two allopatric congeneric oyster species with differential habitat temperatures. These findings unveil the complex and unique phosphorylation-mediated signal transduction mechanisms in marine invertebrates, and further expand our understanding of the evolution and function of established classical pathway crosstalk mechanisms.

cell biology↗

bioRxiv2024

MobiChIP: a compatible library construction method of single-cell ChIP-seq based droplets

In order to illustrate the epigenetic heterogeneity, versatile tools of single-cell ChIP-seq (scChIP-seq) are necessary to meet the convenience and accuracy. Here, we develop MobiChIP, a compatible ChIP-seq library construction method based current sequencing platform with single cell level. As a novel capture strategy, MobiChIP is efficient to capture the fragments from tagmented nuclei of numerous species and execute the mixing of samples from different tissues or species. Especially, this strategy enables the flexible sequencing manipulation and sufficient nucleosome amplification without customized sequencing primers. MobiChIP reveals the landscape of chromatin regulation regions with active(H3K27ac) and repressive(H3K27me3) histone modification markers in peripheral blood mononuclear cells (PBMCs), and accurately unveiled the epigenetic repression of hox gene cluster in PBMCs than ATAC-seq. Meanwhile, we complete the bioinformatics pipeline to integrates the scChIP-seq data and scRNA-seq to illustrate the cellular epigenetic and genetic heterogeneity. One-Sentence SummaryA high-throughput single-cell ChIP-seq based droplet reveals the integration of scRNA-seq data and scChIP-seq data.

molecular biology↗