NMDA receptor-dependent dephosphorylation of serine 387 in Argonaute 2 increases its degradation and affects dendritic spine density and maturation. [Neurobiology]

May 7th, 2018 by Nicolas Paradis-Isler, Jannic Boehm

Argonaute (AGO) proteins are essential components of the microRNA (miRNA) pathway. AGO proteins are loaded with miRNAs to target mRNAs and thereby regulate mRNA stability and protein translation. As such, AGO proteins are important actors in controlling local protein synthesis, for instance, at dendritic spines and synapses. Although miRNA-mediated regulation of dendritic mRNAs has become a focus of intense interest over the past years, the mechanisms regulating neuronal AGO proteins remain largely unknown. Here, using rat hippocampal neurons, we report that dendritic Ago2 is downregulated by the proteasome upon NMDA receptor activation. We found that Ser-387 in Ago2 is dephosphorylated upon NMDA treatment and that this dephosphorylation precedes Ago2 degradation. Expressing Ser-387 phosphorylation-deficient or phosphomimetic Ago2 in neurons, we observed that this phosphorylation site is involved in modulating dendritic spine morphology and postsynaptic density protein 95 (PSD-95) expression in spines. Collectively, our results point toward a signaling pathway linking NMDA receptor-dependent Ago2 dephosphorylation and turnover to postsynaptic structural changes. They support a model in which NMDA receptor-mediated dephosphorylation of Ago2 and Ago2 turnover contribute to the de-repression of mRNAs involved in spine growth and maturation.
  • Posted in Journal of Biological Chemistry, Publications
  • Comments Off on NMDA receptor-dependent dephosphorylation of serine 387 in Argonaute 2 increases its degradation and affects dendritic spine density and maturation. [Neurobiology]

A critical role for nucleoporin 358 (Nup358) in transposon silencing and piRNA biogenesis in Drosophila [RNA]

May 7th, 2018 by Rasesh Y. Parikh, Haifan Lin, Vamsi K. Gangaraju

Piwi-interacting RNAs (piRNAs) are a class of small non-coding RNAs that bind Piwi proteins to silence transposons and to regulate gene expression. In Drosophila germ cells, the Aubergine (Aub)-Argonaute 3 (Ago3)-dependent ping-pong cycle generates most germline piRNAs. Loading of anti-sense piRNAs amplified by this cycle enables Piwi to enter the nucleus and silence transposons. Nuclear localization is crucial for Piwi function in transposon silencing, but how this process is regulated remains unknown. It is also not known whether any of the components of the nuclear pore complex (NPC) directly function in the piRNA pathway. Here, we show that nucleoporin 358 (Nup358) and Piwi interact with each other and that a germline knockdown (GLKD) of Nup358 with short hairpin RNA prevents Piwi entry into the nucleus. The Nup358 GLKD also activated transposons, increased genomic instability, and derailed piRNA biogenesis because of a combination of decreased piRNA precursor transcription and a collapse of the ping-pong cycle. Our results point to a critical role for Nup358 in the piRNA pathway, laying the foundation for future studies to fully elucidate the mechanisms by which Nup358 contributes to piRNA biogenesis and transposon silencing.

Design of glycosylation sites by rapid synthesis and analysis of glycosyltransferases

May 7th, 2018 by Weston Kightlinger

Design of glycosylation sites by rapid synthesis and analysis of glycosyltransferases

Design of glycosylation sites by rapid synthesis and analysis of glycosyltransferases, Published online: 07 May 2018; doi:10.1038/s41589-018-0051-2

The GlycoSCORES method, which involves cell-free protein expression and substrate-site profiling of glycosyltransferase enzymes by SAMDI–MS, enables the identification of glycosylation tags for glycoengineering efforts.
  • Posted in Nat Chem Biol, Publications
  • Comments Off on Design of glycosylation sites by rapid synthesis and analysis of glycosyltransferases

[ASAP] Molecular Mechanism for Folding Cooperativity of Functional RNAs in Living Organisms

May 6th, 2018 by Kathleen A. Leamy, Neela H. Yennawar, Philip C. Bevilacqua

TOC Graphic

Biochemistry
DOI: 10.1021/acs.biochem.8b00345

Publisher Correction: A selective peptide inhibitor of Frizzled 7 receptors disrupts intestinal stem cells

May 4th, 2018 by Aaron H. Nile

Publisher Correction: A selective peptide inhibitor of Frizzled 7 receptors disrupts intestinal stem cells

Publisher Correction: A selective peptide inhibitor of Frizzled 7 receptors disrupts intestinal stem cells, Published online: 04 May 2018; doi:10.1038/s41589-018-0069-5

Publisher Correction: A selective peptide inhibitor of Frizzled 7 receptors disrupts intestinal stem cells
  • Posted in Nat Chem Biol, Publications
  • Comments Off on Publisher Correction: A selective peptide inhibitor of Frizzled 7 receptors disrupts intestinal stem cells

Publisher Correction: Direct multiplex imaging and optogenetics of Rho GTPases enabled by near-infrared FRET

May 4th, 2018 by Daria M. Shcherbakova

Publisher Correction: Direct multiplex imaging and optogenetics of Rho GTPases enabled by near-infrared FRET

Publisher Correction: Direct multiplex imaging and optogenetics of Rho GTPases enabled by near-infrared FRET, Published online: 04 May 2018; doi:10.1038/s41589-018-0070-z

Publisher Correction: Direct multiplex imaging and optogenetics of Rho GTPases enabled by near-infrared FRET
  • Posted in Nat Chem Biol, Publications
  • Comments Off on Publisher Correction: Direct multiplex imaging and optogenetics of Rho GTPases enabled by near-infrared FRET

[ASAP] Modularization and Response Curve Engineering of a Naringenin-Responsive Transcriptional Biosensor

May 3rd, 2018 by Brecht De Paepe, Jo Maertens, Bartel Vanholme, Marjan De Mey

TOC Graphic

ACS Synthetic Biology
DOI: 10.1021/acssynbio.7b00419
  • Posted in ACS Synthetic Biology, Publications
  • Comments Off on [ASAP] Modularization and Response Curve Engineering of a Naringenin-Responsive Transcriptional Biosensor

[ASAP] ICBS 2017 in Shanghai—Illuminating Life with Chemical Innovation

May 1st, 2018 by Qi Zhang, Jingyu Zhang, Evripidis Gavathiotis

ACS Chemical Biology
DOI: 10.1021/acschembio.8b00220

[ASAP] Neuronal Calcium Recording with an Engineered TEV Protease

May 1st, 2018 by Brianna K. O’Neill, Scott T. Laughlin

TOC Graphic

ACS Chemical Biology
DOI: 10.1021/acschembio.8b00130

Shared strategies for β-lactam catabolism in the soil microbiome

April 30th, 2018 by Terence S. Crofts

Shared strategies for β-lactam catabolism in the soil microbiome

Shared strategies for β-lactam catabolism in the soil microbiome, Published online: 30 April 2018; doi:10.1038/s41589-018-0052-1

A β-lactamase, a novel type of amidase, and the phenylacetic acid catabolon comprise a catabolic pathway, revealed by genomic and transcriptomic analysis, that enables multiple soil bacteria to use β-lactam antibiotics as a carbon source.