Dataset Information

Luminescent sensing of conformational integrin activation in living cells

ABSTRACT: Integrins are the major receptors for secreted extracellular matrix, playing crucial roles in several physiological and pathological contexts, such as angiogenesis and cancer. Regulation of the transition between inactive and active conformation is key for integrins to fulfill their functions, and pharmacological control of those dynamics may have therapeutic applications. We created and validated a prototypic luminescent β1 integrin activation sensor (β1IAS) by introducing a split luciferase in a functionally critical extracellular site between the βI and the hybrid domains. Both as recombinant protein and in living cells, β1IAS accurately reports β1 integrin activation in response to (bio)chemical and physical stimuli. A siRNA high-throughput screening on live β1IAS knockin endothelial cells unveiled novel actionable regulators of β1 integrin activation, such as the E3 ligase PJA2 and VEGFB. This split luciferase-based strategy may allow generating activation sensors of other β integrins and receptors.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Kelly Hodge

LAB HEAD: Sara Zanivan

PROVIDER: PXD051442 | Pride | 2025-05-06

REPOSITORIES: Pride

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			Action	DRS
	20230601_KEH_LU_SA_GIV_030523_TMT16_Phospho_f001.raw	Raw
	20230601_KEH_LU_SA_GIV_030523_TMT16_Phospho_f002.raw	Raw
	20230601_KEH_LU_SA_GIV_030523_TMT16_Phospho_f003.raw	Raw
	20230601_KEH_LU_SA_GIV_030523_TMT16_Phospho_f004.raw	Raw
	20230601_KEH_LU_SA_GIV_030523_TMT16_Phospho_f005.raw	Raw

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Luminescent sensing of conformational integrin activation in living cells.

Villari Giulia G Gioelli Noemi N Gino Marta M Zhang Heng H Hodge Kelly K Cordero Francesca F Zanivan Sara S Zhu Jieqing J Serini Guido G

Cell reports 20250217 2

Integrins are major receptors for secreted extracellular matrix, playing crucial roles in physiological and pathological contexts, such as angiogenesis and cancer. Regulation of the transition between inactive and active conformation is key for integrins to fulfill their functions, and pharmacological control of those dynamics may have therapeutic applications. We create and validate a prototypic luminescent β1 integrin activation sensor (β1IAS) by introducing a split luciferase into an activati ...[more]

PMID: 39964812

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