PharmacoSTORM nanoscale pharmacology reveals cariprazine binding on Islands of Calleja granule cells

Nat Commun. 2021 Nov 11;12(1):6505. doi: 10.1038/s41467-021-26757-z.


Immunolabeling and autoradiography have traditionally been applied as the methods-of-choice to visualize and collect molecular information about physiological and pathological processes. Here, we introduce PharmacoSTORM super-resolution imaging that combines the complementary advantages of these approaches and enables cell-type- and compartment-specific nanoscale molecular measurements. We exploited rational chemical design for fluorophore-tagged high-affinity receptor ligands and an enzyme inhibitor; and demonstrated broad PharmacoSTORM applicability for three protein classes and for cariprazine, a clinically approved antipsychotic and antidepressant drug. Because the neurobiological substrate of cariprazine has remained elusive, we took advantage of PharmacoSTORM to provide in vivo evidence that cariprazine predominantly binds to D3 dopamine receptors on Islands of Calleja granule cell axons but avoids dopaminergic terminals. These findings show that PharmacoSTORM helps to quantify drug-target interaction sites at the nanoscale level in a cell-type- and subcellular context-dependent manner and within complex tissue preparations. Moreover, the results highlight the underappreciated neuropsychiatric significance of the Islands of Calleja in the ventral forebrain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Female
  • Islands of Calleja / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Piperazines / pharmacology
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Dopamine D3 / metabolism


  • Piperazines
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • cariprazine