Campari2 genomic interrogation of homeostatic calcium activity identifies TIM1 as a negative regulator of T cell function
Year: 2025
Type: article
Abstract: Calcium signals regulate crucial cellular functions yet many genes coding for Ca 2+ handling proteins remain unknown as their identification relies on low-throughput single-cell approaches. Here we describe a method to measure Ca 2+ activity using CaMPARI2, flow cytometry and pooled genome interrogation. CAMPARI2 screen (CaMP-Screen) identified enhancers and inhibitors of homeostatic Ca 2+ activity, highlighting a predominant role for store-operated Ca 2+ entry (SOCE) and lipid signalling pathways. Genes reducing basal Ca 2+ activity were linked to Prader Willy syndrome, T cell dysfunction, and deafness. Silencing of HAVCR1 gene, coding for T cell transmembrane immunoglobulin and mucin (TIM1), enhanced Ca 2+ signals in T cells and promoted signaling under resting but not after TCR engagement. Our findings establish CaMP-Screen as an efficient detector of low-amplitude Ca 2+ signals and identify new genes associated to pathologies that regulate Ca 2+ homeostasis, reporting TIM1 as a negative regulator of Ca 2+ signals driving T cell function.
Source: Cell Calcium
Institution: University of Geneva
Language: English
Topic: Ion Channels and Receptors
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,950
OpenAlex ID: W4410458481