Check out the stunning movie by @xianglejerry.bsky.social from @wumin-lab.bsky.social, the winner of the 2024 ASCB Video Contest! Traveling waves of FBP17-EGFP at the cortex of immune mast cells #ASCB2024 @ascbiology.bsky.social

11/Can Ca²⁺ release at ER-PM junctions activate Ca²⁺-dependent intracellular signaling? Upon stimulation, pCaMKII accumulates in spine's heads and JPH3 contacts along dendrites, suggesting that ER-PM junctions serve as preferential sites for Ca²⁺-dependent intracellular signaling along dendrites.

10/ One of the most exciting aspects was that local spine activation triggers Ca²⁺ release from the ER via RyRs at these ER-PM contact sites. Contact sites support Ca²⁺ signal propagation over distances 100x greater than spine’s head, revealing a mechanism for amplifying and distributing signals.

9/ These junctions are populated with Ca²⁺ tuners and responders. Among them, on the ER membrane, we found that the Ca²⁺-activated Ca²⁺ release channel, RyR, is enriched at JPH3 junctions, where it is maintained in nanometer proximity to plasma membrane Ca²⁺ sources.

7/ We found that JPH3 plays a critical role in controlling the positioning and accumulation of voltage-gated ion channels at ER-PM junctions. These data reveal a new fundamental role for the ER in regulating the positioning of voltage-gated ion channels at the plasma membrane of dendrites.

6/ These junctions are populated by the ER-PM tethering protein JPH3.

5/ and in neurons of the fly brain.

4/ These transverse ER elements protrude and form regular connections with the plasma membrane. Using volumetric EM reconstructions, we confirmed this in vivo in the mouse hippocampus.

3/ Using live 3D lattice SIM imaging, we observed that along proximal and medial dendrites, longitudinal ER elements are connected by very regularly interspersed.
transverse ER elements.

2/We reveal how a unique organization of ER-PM contact sites shapes the ER in dendrites into a ladder-like structure. These periodic ER-PM contacts act as local, spatial, and temporal amplifiers for Ca²⁺-dependent signaling.

I am super excited to share our article addressing a longstanding question in neurobiology: how Ca²⁺ signaling cascades initiated at dendritic spines operate at a distance. Check it out here: authors.elsevier.com/sd/article/S... @cp-cell.bsky.social.

Kicking off here with some old but gold movies showing ER-lysosome interactions triggered by blue-light excitation of the light-sensitive protein eMags. A shining example of how light can control cellular dynamics! 💡🧫✨