October 24, 2020

Synaptic anchoring of the endoplasmic reticulum depends on myosin V and caldendrin activity

Excitatory synapses of principal hippocampal neurons are frequently located on dendritic spines. The dynamic strengthening or weakening of individual inputs results in a great structural and molecular diversity of dendritic spines. Active spines with large Ca2+ transients are frequently invaded by a single protrusion from the endoplasmic reticulum (ER), which is dynamically transported into and out of spines by the actin-based motor myosin V. An increase in synaptic strength often correlates with stable anchoring of the ER, followed by the formation of the spine apparatus organelle. Here we show that synaptic ER stabilization depends on the interplay of two Ca2+-binding proteins: calmodulin serves as a light chain of myosin V and activates the motor function, whereas caldendrin acts as an inhibitor which transforms myosin into a stationary F-actin tether. Together, they provide a Ca2+-sensing module for fine-tuning myosin V activity and thereby regulate the formation of the spine apparatus in a subset of active dendritic spines.

 bioRxiv Subject Collection: Neuroscience

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