Molecular recording of calcium signals via calcium-dependent proximity labeling

J. Wren Kim, Adeline J.H. Yong, Erin E. Aisenberg, Joseph H. Lobel, Wei Wang, Ted M. Dawson, Valina L. Dawson, Ruixuan Gao, Yuh Nung Jan, Helen S. Bateup, Nicholas T. Ingolia

Research output: Contribution to journalArticlepeer-review


Calcium ions serve as key intracellular signals. Local, transient increases in calcium concentrations can activate calcium sensor proteins that in turn trigger downstream effectors. In neurons, calcium transients play a central role in regulating neurotransmitter release and synaptic plasticity. However, it is challenging to capture the molecular events associated with these localized and ephemeral calcium signals. Here we present an engineered biotin ligase that generates permanent molecular traces in a calcium-dependent manner. The enzyme, calcium-dependent BioID (Cal-ID), biotinylates nearby proteins within minutes in response to elevated local calcium levels. The biotinylated proteins can be identified via mass spectrometry and visualized using microscopy. In neurons, Cal-ID labeling is triggered by neuronal activity, leading to prominent protein biotinylation that enables transcription-independent activity labeling in the brain. In summary, Cal-ID produces a biochemical record of calcium signals and neuronal activity with high spatial resolution and molecular specificity. (Figure presented.)

Original languageEnglish (US)
Pages (from-to)894-905
Number of pages12
JournalNature chemical biology
Issue number7
StatePublished - Jul 2024

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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