PPP3/calcineurin-dependent TFEB dephosphorylation mechanism

Exploratory Score: 0.800 Price: $0.50 motoneuron degeneration neuronal cell lines Status: proposed

What This Experiment Tests

Exploratory experiment designed to discover new patterns targeting PPP3CB in neuronal cell lines. Primary outcome: TFEB phosphorylation status and nuclear localization

Description

This experiment investigated the molecular mechanism linking lysosomal membrane permeabilization to TFEB activation. The study examined calcium-dependent phosphatase PPP3/calcineurin activation following trehalose-induced lysosomal damage, leading to TFEB dephosphorylation and subsequent nuclear translocation. The researchers used calcium imaging, phosphatase activity assays, and immunofluorescence to demonstrate that lysosomal calcium release activates calcineurin, which then dephosphorylates TFEB, allowing its nuclear translocation and transcriptional activity.

TARGET GENE
PPP3CB
MODEL SYSTEM
neuronal cell lines
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
calcium-calcineurin-TFEB signaling pathway
SOURCE
extracted_from_pmid_30335591
PRIMARY OUTCOME
TFEB phosphorylation status and nuclear localization

Scoring Dimensions

Info Gain 0.00 (25%) Feasibility 0.00 (20%) Hyp Coverage 0.00 (20%) Cost Effect. 0.00 (15%) Novelty 0.00 (10%) Ethical Safety 0.00 (10%) 0.800 composite

📖 Wiki Pages

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Protocol

Calcium imaging, immunofluorescence microscopy, western blotting for phospho-TFEB, subcellular fractionation, phosphatase activity assays

Expected Outcomes

Lysosomal calcium release would activate calcineurin, leading to TFEB dephosphorylation and nuclear translocation

Success Criteria

Demonstration of calcium-dependent TFEB dephosphorylation and nuclear translocation that can be blocked by calcineurin inhibitors

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