4.6 Article

Luminescence-activated nucleotide cyclase regulates spatial and temporal cAMP synthesis

期刊

JOURNAL OF BIOLOGICAL CHEMISTRY
卷 294, 期 4, 页码 1095-1103

出版社

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.AC118.004905

关键词

cyclic AMP (cAMP); bioluminescence; optogenetics; fluorescence resonance energy transfer (FRET); signaling; second messenger; cell proliferation; thyroid; bPAC; compartmentalization; microdomains; nano-luciferase

资金

  1. National Institutes of Health NIDDK grant
  2. National Institutes of Health NIGMS grant
  3. Molecular Pharmacology Training Program of the University of Pittsburgh under National Institutes of Health Awards [R01-GM09975, R01-DK102495, R01-DK111427, R01-DK116780]
  4. National Institutes of Health [T32-GM008424, T32-GM00842419, T32-GM00842420, T32-GM00842421]
  5. Winstar Morris' Cotswold Foundation Fellowship

向作者/读者索取更多资源

cAMP is a ubiquitous second messenger that regulates cellular proliferation, differentiation, attachment, migration, and several other processes. It has become increasingly evident that tight regulation of cAMP accumulation and localization confers divergent yet specific signaling to downstream pathways. Currently, few tools are available that have sufficient spatial and temporal resolution to study location-biased cAMP signaling. Here, we introduce a new fusion protein consisting of a light-activated adenylyl cyclase (bPAC) and luciferase (nLuc). This construct allows dual activation of cAMP production through temporally precise photostimulation or chronic chemical stimulation that can be fine-tuned to mimic physiological levels and duration of cAMP synthesis to trigger downstream events. By targeting this construct to different compartments, we show that cAMP produced in the cytosol and nucleus stimulates proliferation in thyroid cells. The bPAC-nLuc fusion construct adds a new reagent to the available toolkit to study cAMP-regulated processes in living cells.

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