Proximity proteomics of synaptopodin provides insight into the molecular composition of the spine apparatus of dendritic spines

Hanieh Falahati, Yumei Wu, Vanessa Feuerer, Hans Georg Simon, Pietro De Camilli*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


The spine apparatus is a specialized compartment of the neuronal smooth endoplasmic reticulum (ER) located in a subset of dendritic spines. It consists of stacks of ER cisterns that are interconnected by an unknown dense matrix and are continuous with each other and with the ER of the dendritic shaft. While this organelle was first observed over 60 y ago, its molecular organization remains a mystery. Here, we performed in vivo proximity proteomics to gain some insight into its molecular components. To do so, we used the only known spine apparatus–specific protein, synaptopodin, to target a biotinylating enzyme to this organelle. We validated the specific localization in dendritic spines of a small subset of proteins identified by this approach, and we further showed their colocalization with synaptopodin when expressed in nonneuronal cells. One such protein is Pdlim7, an actin binding protein not previously identified in spines. Pdlim7, which we found to interact with synaptopodin through multiple domains, also colocalizes with synaptopodin on the cisternal organelle, a peculiar stack of ER cisterns resembling the spine apparatus and found at axon initial segments of a subset of neurons. Moreover, Pdlim7 has an expression pattern similar to that of synaptopodin in the brain, highlighting a functional partnership between the two proteins. The components of the spine apparatus identified in this work will help elucidate mechanisms in the biogenesis and maintenance of this enigmatic structure with implications for the function of dendritic spines in physiology and disease.

Original languageEnglish (US)
Article numbere2203750119
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number42
StatePublished - Oct 18 2022


  • Pdlim7
  • dendritic spine
  • iBioID
  • in vivo proximity proteomics
  • spine apparatus

ASJC Scopus subject areas

  • General


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