Caldendrin and myosin V regulate synaptic spine apparatus localization via ER stabilization in dendritic spines

EMBO J. 2022 Feb 15;41(4):e106523. doi: 10.15252/embj.2020106523. Epub 2021 Dec 22.


Excitatory synapses of principal hippocampal neurons are frequently located on dendritic spines. The dynamic strengthening or weakening of individual inputs results in structural and molecular diversity of dendritic spines. Active spines with large calcium ion (Ca2+ ) transients are frequently invaded by a single protrusion from the endoplasmic reticulum (ER), which is dynamically transported into spines via the actin-based motor myosin V. An increase in synaptic strength correlates with stable anchoring of the ER, followed by the formation of an organelle referred to as the spine apparatus. Here, we show that myosin V binds the Ca2+ sensor caldendrin, a brain-specific homolog of the well-known myosin V interactor calmodulin. While calmodulin is an essential activator of myosin V motor function, we found that caldendrin acts as an inhibitor of processive myosin V movement. In mouse and rat hippocampal neurons, caldendrin regulates spine apparatus localization to a subset of dendritic spines through a myosin V-dependent pathway. We propose that caldendrin transforms myosin into a stationary F-actin tether that enables the localization of ER tubules and formation of the spine apparatus in dendritic spines.

Keywords: caldendrin; endoplasmic reticulum; myosin; spine apparatus; synapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Calmodulin / metabolism
  • Dendritic Spines / metabolism*
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum, Smooth / metabolism
  • HEK293 Cells
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Humans
  • Mass Spectrometry
  • Mice, Knockout
  • Myosin Type V / genetics
  • Myosin Type V / metabolism*
  • Protein Interaction Domains and Motifs
  • Rats, Wistar


  • Actins
  • Calcium-Binding Proteins
  • Calmodulin
  • Myosin Type V
  • Ca2+-binding protein-1