Watanabe Lab @JHU

Here’s a nice article from the @hopkinsmedicine.bsky.social news room, covering the work!

Happy to share our new paper, just published in @cellpress.bsky.social. We show that our zap&freeze approach can be used in human brain tissues to study synaptic membrane dynamics! Our brain is ultrafast after all! nam02.safelinks.protection.outlook.com?url=https%3A...

Johns Hopkins scientists discover how a protein organizes message-carrying "bubbles" in brain synapses—advancing understanding of memory formation and learning. www.oneneurojhu.org/...
@watanabelab.bsky.social

I am incredibly honored to receive this award! But now that I am behind the computer all day, this really is for the team! Congrats to the Watanabe lab!

MBL Announces Largest Ever Gift for Its Renowned Biological Education and Research Programs | Marine Biological Laboratory Cell Biology Researcher Mark Terasaki’s $25 Million Unrestricted Gift Will Support Operations and Infrastructure Contact: Samantha Cummis scummis@mbl.edu; 973.800.4119

We're thrilled to announce the largest private gift in our 137-year history: a $25 million unrestricted donation from MBL Whitman Scientist Mark Terasaki.

His extraordinary generosity will bolster our renowned research and education programs. 🔬

Learn more: bit.ly/452WL1m

A tactile discrimination task to study neuronal dynamics in freely-moving mice - Nature Communications Task paradigms allowing studies on the core ethological function of the whiskers are lacking. Authors here present a task for freely moving mice that enables the study of how the brain processes touch...

We unrestrained mice to study how they use their whiskers to learn a discrimination task. www.nature.com/articles/s41...

Intersectin and endophilin condensates prime synaptic vesicles for release site replenishment - Nature Neuroscience Time-resolved electron microscopy reveals that intersectin-1 and endophilin A1 condensates hold replacement synaptic vesicles close to release sites. Without this, replacement vesicles are unavailable...

Intersectin and endophilin condensates prime synaptic vesicles for release site replenishment

@watanabelab.bsky.social

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

@ogunmowo.bsky.social led the work with the help from Renee Pepper, Chin Patel (supported by Brady Maher), Annie Ho, and Sumana Raychaudhuri. Congrats to all!

We sincerely thank our wonderful collaborators, Ben Cooper, Ira Milosevic and Dragomir Milovanovic, and their lab members (Christian Hoffmann, Han Wang, Sindhuja Gowrisankaran, Johanna Idel).

Speculatively, Itsn1-EndoA1 condensates may be acting like pickering agents, stabilizing the active zone phase and the vesicle cluster phase at rest, and upon calcium influx, enabling the transition of vesicles across different phases. But more work is needed!

In the absence of Itsn1 or EndoA1, fewer vesicles are available around this region, and consequently, new synaptic vesicles cannot occupy the vacated release sites rapidly and synapses depress faster during the train of stimuli in the mutants.

STED images showing localization of Intersectin 1 and Synapsin 1 relative to the active zone, marked by Bassoon

Super excited to share that our new study is published @natneuro.nature.com today!! Here we show that intersectin and endophilin form condensates between the active zone and the reserve pool and maintain synaptic vesicles near the active zone for rapid replenishment.

rdcu.be/evi5y

Beyond Clathrin: Decoding the Mechanism of Ultrafast Endocytosis - PubMed Endocytosis in nonneuronal cells requires gradual recruitment of proteins to endocytic sites for inducing membrane curvature and forming scaffolds around the neck of endocytic pits. This recruitment p...

We wrote a review article on ultrafast endocytosis and its mechanisms and relevance to diseases. Enjoy! pubmed.ncbi.nlm.nih.gov/40062769/

A new preprint alert from the lab!! Evidence for ultrafast endocytosis in inhibitory synapses!! www.biorxiv.org/content/10.1...

A weekend fun with the lab! Welcoming four new members to the lab!!

Excited to share our new preprint "Dynamic nanoscale architecture of synaptic vesicle fusion in mouse hippocampal neurons" www.biorxiv.org/content/10.1...

We combine optogenetic stimulation of neurons with in situ cryo-ET to characterize membrane dynamics during synaptic vesicle fusion ❄️🔬⏱️

New preprint from the MemTraS team ! www.biorxiv.org/content/10.1...
Great collaboration with @fronzeslab.bsky.social and Vladan Lucic to determine the first cryo electron tomography images of dopamine "synapses" extracted from adult mouse brain.

Challenging the Axon’s Classic Shape Forget the traditional tubular shape—researchers are investigating a pearl-on-a-string formation for axons, unlocking new insights into neural signaling in health and disease.

another piece, covering our work! Thanks to Laura Tran at the Scientist!!
www.the-scientist.com/challenging-...

📆Deadline extension alert!📆

The last day to submit applications for the MBL's 2025 Neurobiology course has been moved to February 3. Don't miss your opportunity to apply!

Read more: bit.ly/3C2psks
#ScienceStartsHere

and axons in human brain!? yep, it's pearled!!

This was led by Chelsy_Eddings! assisted by Xiomara McDonald, and wonderful collaboration with David Nauen, Stan William (neurosurgeon), Minghua Fan&Paul Worley, Yuuta Imoto, Kie Itoh, @HopkinsMedicine and Kristina Lippmann&Jens Eilers! Thanks all for their efforts!!

and the mechanism? seems to be conserved! A brain-enriched splice variant of Dynamin 1 is pre-recruited to the endocytic zone, just like we showed in mouse neurons.

pubmed.ncbi.nlm.nih.gov/35809574/

another preprint to end 2024!

Wondered how synaptic vesicles are recycled in human brains? and whether you can use human brain tissues to address it? You bet! We used live human brain slices and demonstrated that ultrafast endocytosis does it!! www.biorxiv.org/content/10.1...

The message-sending part of neurons may be blobby, not smooth Axons can be shaped like strings of pearls, research in mice and people show. How that shape may influence brain signaling is not yet clear.

Here's another article, covering our work!!
www.sciencenews.org/article/axon...

Study finds axons are not the cylindrical tubes pictured in books but more like pearls on a string.
Article Link: www.oneneurojhu.org/2024/12/10/s...

“These findings challenge a century of understanding about axon structure,” says lead researcher Shigeki Watanabe, Ph.D. @watanabelab.bsky.social

Thank you! Those are exact questions we are trying to address rn!!

Would be cool to figure out where NaV and KV are located relative to these structures!

Fixation by PFA can affect cytoskeletal elements, protein localization, and membrane architecture and properties. Osmolarity effect cannot be excluded.. so it will be difficult to pinpoint it…

A String of Pearls: Study Challenges Long-held Beliefs about Nerve Cell Shape and Function | Marine Biological Laboratory WOODS HOLE, Mass. -- In a provocative new study, scientists challenge a fundamental tenet in neuroscience about the shape of axons -- the long, thin filaments radiating from nerve cells that transmit ...

This new study, led by Shigeki Watanabe and partially conducted in the MBL’s Neurobiology course, challenges a fundamental tenet in neuroscience about the shape of axons and proposes a new model for understanding how information is transmitted in the brain. #science 🧪 🧠

hard to predict since cholesterol contributes to more than just the membrane fluidity... also, lipid saturation levels could be altered... interesting to look at!!