Asset Details
Do you wish to reserve the book?
Endoplasmic Reticulum Geometry Dictates Neuronal Bursting via Calcium Store Refill Rates and Exposes Selective Neuronal Vulnerability
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Endoplasmic Reticulum Geometry Dictates Neuronal Bursting via Calcium Store Refill Rates and Exposes Selective Neuronal Vulnerability
Do you wish to request the book?
Endoplasmic Reticulum Geometry Dictates Neuronal Bursting via Calcium Store Refill Rates and Exposes Selective Neuronal Vulnerability
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Endoplasmic Reticulum Geometry Dictates Neuronal Bursting via Calcium Store Refill Rates and Exposes Selective Neuronal Vulnerability
2026
Overview
The endoplasmic reticulum (ER)’s continuous morphology is tightly controlled by ER‐shaping proteins, whose genetic or expression defects drive a spectrum of neurodegenerative disorders from Hereditary Spastic Paraplegia to Alzheimer's disease. Why perturbations in ER morphology manifest specifically in neurons remains unknown. Here, by coupling visualisation of global sub‐Hz firing bursts to ER ultrastructural manipulations in human inducible Pluripotent Stem Cells (hiPSC)‐derived cortical neurons, alongside physical simulations, we establish a key ER structure‐function principle: neuronal ER architecture dictates Ca2+ replenishment speed. Altering ER structure hinders network ER luminal connectivity and Ca2+ propagation from refill points at plasma membrane contact sites, impairing the ER's capability to supply repetitive Ca2+ bursts. The ER morpho‐regulatory control of Ca2+ refill speed thus constitutes a switch on neuronal activity. Further, perturbed ER shape also abolishes Ca2+ firing and contraction in primary skeletal muscle cells. These results expose the selective vulnerability of Ca2+‐firing cells to ER structural disruptions, rationalizing ER dysfunction in neurodegeneration and unveiling a new role for the continuous ER morphology that could apply universally to Ca2+‐firing cells. The ER's continuous tubular network is maintained by ER‐shaping proteins whose mutation or dysregulation contributes to neurodegenerative diseases. Here, we show that ER morphology sets the speed of Ca2+ store replenishment between firing events. Disrupting ER continuity slows intra‐ER Ca2+ redistribution from extracellular refill (SOCE) sites, driving burst rundown and functional failure—offering a mechanism for selective neuronal vulnerability to ER defects.
Publisher
John Wiley & Sons, Inc,Wiley
