Amreen Mughal @amreenmughal

TMC1 and TMC2 are cholesterol-dependent scramblases that regulate membrane homeostasis in auditory hair cells TMC1 and TMC2, the pore-forming subunits of the mechanoelectrical transduction (MET) complex in inner ear sensory hair cells, are essential for auditory and vestibular function. Pathogenic mutations in TMC1 are a leading cause of genetic hearing loss, but their underlying cellular mechanisms remain poorly understood. Here, we reveal that TMC1 and TMC2 are cholesterol-regulated lipid scramblases whose activity modulates plasma membrane asymmetry. Using reconstituted proteoliposomes and molecular dynamics simulations, we demonstrate that both proteins facilitate phospholipid translocation across membrane bilayers, a process tuned by cholesterol and enhanced by deafness-causing TMC1 mutations. We show that this scramblase activity correlates with TMC1-dependent externalization of phosphatidylserine and membrane blebbing in murine auditory hair cells, linking TMC1-dependent membrane homeostasis dysregulation to auditory sensory cell pathology. These findings identify TMCs as a novel family of lipid scramblases, advancing our understanding of MET complex biology and offering mechanistic insight into membrane-driven forms of hereditary deafness. ### Competing Interest Statement The authors have declared no competing interest. National Institute on Deafness and Other Communication Disorders, https://ror.org/04mhx6838, DC000096, DC015271

Excited to share our first pre-print from the new SSPB section at the NIDCD!🥳
We hope you find it interesting and inspiring for future research. Thanks to our team, colleagues, mentors and collaborators 🔥 💪 🙏 .
Take a look—and stay tuned for more!
www.biorxiv.org/content/10.1...

07.07.2025 15:28 — 👍 2 🔁 1 💬 0 📌 0

Showing how a precapillary sphincter dilates during high blood pressure

🐭🧠 #PrecapillarySphincters (PS) at the #arteriole–#capillary junction rapidly dilate ~30% in seconds during #SensoryStimulation—regulating #capillary #BloodFlow dynamically. Here we investigated whether they protect downstream microvessels during abrupt #BloodPressure surges 🧪🧵

10.06.2025 19:38 — 👍 19 🔁 8 💬 2 📌 2

Congrats @sorengrubb.bsky.social and team :)

10.06.2025 19:42 — 👍 1 🔁 0 💬 1 📌 0

Congrats John and team :)

03.05.2025 03:01 — 👍 2 🔁 0 💬 1 📌 0

Congrats :)

02.05.2025 14:21 — 👍 1 🔁 0 💬 1 📌 0

Congratulations 🎊

30.04.2025 14:38 — 👍 1 🔁 0 💬 0 📌 0

Congratulations to you and your team 🎊

25.03.2025 19:34 — 👍 1 🔁 0 💬 1 📌 0

I am actively looking for a research scientist position or research administration role within the Raleigh-Durham (RDU) area! Please reach out if my background and skillset might fit your labs needs :-) Lots of experience with preclinical models, translational neuroscience, and behavioral analyses!

16.02.2025 15:49 — 👍 124 🔁 84 💬 4 📌 8

Electrifying the brain capillary Ca2+ signal | PNAS Electrifying the brain capillary Ca2+ signal

Check out this editorial written for a beautiful work by MArk Nelson's Lab on electro-calcium coupling and control of the neurovascular unit.

www.pnas.org/doi/10.1073/...

21.01.2025 15:49 — 👍 8 🔁 4 💬 1 📌 0

Congratulations 🎊

16.01.2025 14:18 — 👍 1 🔁 0 💬 1 📌 0

Electrocalcium coupling in brain capillaries: Rapidly traveling electrical signals ignite local calcium signals | PNAS The routing of blood flow throughout the brain vasculature is precisely controlled by mechanisms that serve to maintain a fine balance between loca...

🤩 🤩 doi.org/10.1073/pnas...

12.12.2024 01:32 — 👍 18 🔁 5 💬 1 📌 0

Thank you, highly appreciate it :)

12.12.2024 13:25 — 👍 1 🔁 0 💬 0 📌 0

Check our illustration of the Electro-Calcium Coupling

12.12.2024 01:07 — 👍 1 🔁 0 💬 0 📌 0

New publication Alert: Delighted to share our latest work. We describe a unique relationship between electrical and Calcium signaling; 'Electro-Calcium Coupling' in brain capillary endothelial cells.
www.pnas.org/doi/10.1073/...

11.12.2024 23:35 — 👍 16 🔁 2 💬 2 📌 0

Congratulations 🎊

10.12.2024 13:04 — 👍 0 🔁 0 💬 1 📌 0

Congratulations 🎊

09.12.2024 17:43 — 👍 0 🔁 0 💬 1 📌 0

Yes, please. Thank you 😊

06.12.2024 21:17 — 👍 1 🔁 0 💬 1 📌 0

I am delighted to share the work of my amazing student Dominic Isaacs! Out today in PNAS (www.pnas.org/doi/10.1073/...), Dom beautifully used optogenetics to show that thin-strand pericytes in the brain can send long-range electrical signals to control arteriole diameter and brain blood flow.

04.12.2024 19:05 — 👍 29 🔁 8 💬 5 📌 1

Congratulations :)

04.12.2024 19:57 — 👍 0 🔁 0 💬 0 📌 0

Join us!!
We are looking for a postdoc candidate to join our team. We study neurovascular coupling mechanisms in the basic physiology and in the models of Vascular Dementia. Learn more: research.ninds.nih.gov/mughal-lab
#Postdocjobs #Neurovascular #Physiology
Thank you for the repost/share :)

24.11.2024 03:40 — 👍 7 🔁 1 💬 0 📌 0

Please add me. Thanks :)

21.11.2024 17:36 — 👍 1 🔁 0 💬 1 📌 0

Yes, please

18.11.2024 13:06 — 👍 4 🔁 0 💬 0 📌 0

Please add me :)

16.11.2024 22:35 — 👍 0 🔁 0 💬 0 📌 0

Congratulations 🙂

16.11.2024 01:27 — 👍 1 🔁 0 💬 1 📌 0

I am a Stadtman Tenure-Track Investigator at the NIH-IRP (NINDS-Stroke Branch + NHLBI-TVM). I lead 'Neurovascular Research Unit' and we study blood flow regulation in the brain & clearance of metabolic by-products in the health and mouse models of VCID. Learn more: research.ninds.nih.gov/mughal-lab

16.11.2024 00:34 — 👍 10 🔁 1 💬 0 📌 0

Thank you @siegenthalerlab.bsky.social . Super excited to become a part of the growing community :)

15.11.2024 12:54 — 👍 1 🔁 0 💬 0 📌 0

Yes please. Thank you :)

12.11.2024 13:24 — 👍 1 🔁 0 💬 0 📌 0

Amreen Mughal

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