Ed Twomey

Calcium and magnesium in the pore of NMDA receptors!

Lipids play an unexpected role. The hydration shells of Ca2+ and Mg2+ could be the difference between permeation and block. So much physiology in the energetics of H2O.

Very stimulating work! Congrats @lab-furukawa.bsky.social

#iglurs

Cofilin Inhibition Ameliorates PIEZO2 and AMPA Dysfunction in a Mouse Model of Angelman Syndrome Angelman syndrome (AS) is a neurogenetic disorder characterized by motor coordination and cognitive deficits. In AS, hippocampal neurons show reduced filamentous (F-)actin, a decrease we also reported...

Our new Journal of Neuroscience paper "Cofilin Inhibition Ameliorates PIEZO2 and AMPA Dysfunction in a Mouse Model of Angelman Syndrome (AS)” is out: www.jneurosci.org/content/45/4... 1/6

During these uncertain times, I’m very happy to see that my institution, @scripps.edu has an open tenure-track Assistant Professor position. Any field in Chemistry or Biology is welcome. I’d especially love to see fellow neuroscientists apply. Please repost!

apply.interfolio.com/174756

My OpEd piece in US News & World Report, about not wanting my life to be book-ended by two fascist regimes and about the state of higher education in this country,

www.usnews.com/opinion/arti...

has now been republished in German translation by JOSHA:

josha-journal.org/en/categorie...

Congrats to the winners! Its notable that Omar Yaghi was a refugee. Refugees and immigrants once again making American science great!

Senior Director - Scientific Officer Primary Work Address: 4000 Jones Bridge Road, Chevy Chase, MD, 20815 Current HHMI Employees, click here to apply via your Workday account. The Howard Hughes Medical Institute (HHMI) advances the disco...

Great Job - Great Colleagues - Great Science👍
Help us pick the next generation of @hhmi.org Investigators, Freeman Hrabowski Scholars, Hanna Gray Fellows, Gilliam Fellows
Relocation to DC is required, perfect for academic PIs looking for their next chapter
hhmi.wd1.myworkdayjobs.com/External/job...

#TeamTomo ❄️🔬 meets #MassSpec Imaging 🧬🔬. Super cool, and great potential for EM grids with mixes of different cell types. For example -- environmental samples! @embltrec.bsky.social 🌍 🧪

Enhanced PIEZO1 function contributes to the pathogenesis of sickle cell disease | PNAS Sickle cell disease (SCD), an inherited blood disorder caused by a mutation in the β-globin gene, is characterized by sickle erythrocytes that are ...

Our new PNAS paper "Enhanced PIEZO1 function contributes to the pathogenesis of sickle cell disease" is out: www.pnas.org/doi/10.1073/... 1/3

Congrats!!!

Cryo-EM snapshots of NMDA receptor activation illuminate sequential rearrangements Opening of the NMDA receptor involves bending of the helices lining the ion channel gate.

Cryo-EM snapshots of NMDA receptor activation illuminate sequential rearrangements | Science Advances www.science.org/doi/10.1126/...

PIEZO channels link mechanical forces to uterine contractions in parturition Mechanical forces are extensively involved in pregnancy and parturition, but their precise roles and mechanisms remain poorly understood. Here, we identify mechanically activated ion channels PIEZO1 a...

New preprint alert! The uterus expands ~500-fold in pregnancy, yet we know little about how pressures are sensed. Led by @yunxiao-dr.bsky.social, we show PIEZOs are required for contractions and birth in mice, with dual roles of PIEZO1 in muscle and PIEZO2 in neurons
www.biorxiv.org/content/10.1...

Thank you! Much appreciated. Hope you are doing well!

Thank you, John!

Thank you, Sasha!

Thank you!

#Neuroscience #BrainDiscovery #NewTherapies #DeltaReceptor #Glutamate #ScienceBreakthrough #SynapticTransmission #CryoEM #iGluR

This completely rewrites the textbooks on how brains process information, and completes the iGluR family. An additional fun fact is that despite being glutamate receptors, these are not activated by glutamate, but rather the neurotransmitters GABA and D-serine.

Why is this important? Despite their role in brain health, neurological disease, and psychiatric disorders, no treatments have been developed to target GluDs because their intrinsic mechanisms have been unknown. This work lifts that veil to open new doors for therapeutic development.

Today, we report the solving of this mystery: delta receptors are actually ligand-gated ion channels - tiny biological switches that power brain activity and learning by turning neurotransmitters into electrical signal.

For decades, scientists have puzzled over the delta glutamate receptors (GluDs), mysterious proteins in the brain that are vital for synapse formation and maintenance, and are directly implicated in psychiatric and neurological disorders, but whose true function was unknown.

🚨🧠🔬 A major breakthrough in molecular neuroscience:

I am excited to share a new story from our lab, published in accelerated format today by @nature.com:

"Delta-type glutamate receptors are ligand-gated ion channels"

Read more here (free article link): rdcu.be/eGIKz

This is fantastic - glad to see it out!

Post an image from your summer that confers peace.

(from the Telluride ion channels workshop)

Upper - cryo-EM reconstruction of stomatin AQP1 complex. Lower - reconstruction of stomatin-UT-B complex.

Happy to share a new preprint from the Clarke & Vallese (@fravallese.bsky.social) labs reporting #cryoem structures of two RBC stomatin complexes – with AQP1 & UT-B - continuing the SPFH theme from our recent vault preprint! This was a fun one and has been cooking for a while - read on for more! ⬇️

Leopard-EM: An extensible 2DTM package to accelerate in situ structural biology The ability to generate high-resolution views of cells with cryogenic electron microscopy (cryo-EM) can reveal the molecular mechanisms of biological processes in their native cellular context. The re...

First pre-print from the Lucas Lab led by Matthew Giammar and @joshdcryoem.bsky.social online today! We develop a new, extensible Python implementation of 2DTM and apply it to build pixel size optimization, constrained search and characterize molecular motions in situ www.biorxiv.org/content/10.1...

This is not who we are. We must join together to call this out, to make more people understand what is happening and work to stop it.

Activity-driven proprioceptive synaptic refinement in the developing spinal cord by complement signaling mechanisms Proprioceptive group Ia afferents detect muscle stretch to guide effortless and purposeful movement and make monosynaptic connections with spinal α–motor neurons to mediate reflexes, such as the stret...

Happy to share the my lab's latest preprint, where we investigated sensorimotor circuit formation in the developing spinal cord. We show that proprioceptive axons target motor neurons in neighboring spinal segments to give rise to intersegmental reflex responses.
www.biorxiv.org/content/10.1...

Activation of kainate receptor GluK2–Neto2 complex - Nature Structural & Molecular Biology Gangwar et al. present cryo-electron microscopy structures of GluK2 kainate receptors with auxiliary subunit Neto2 and reveal the basis of receptor activation.

Kainate receptor modulation by Neto including an open state. Surprising, to me: I would never have imagined that Neto works like a membrane-tethered lectin (ConA). Auxiliary proteins influence dimer-dimer interactions, as we and others also showed in AMPARs.

#iGluRs

www.nature.com/articles/s41...

How Many Times Can Science Funding Be Canceled? Whether or not Congress cuts NIH’s budget, the Trump administration has devastated its ability to operate.

New Story in The Atlantic about NIH

www.theatlantic.com/health/archi...

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