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Elife. 2015 Dec 8;4. pii: e10024. doi: 10.7554/eLife.10024.

Near-infrared photoactivatable control of Ca(2+) signaling and optogenetic immunomodulation.

Author information

1
Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, United States.
2
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States.
3
Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, China.
4
Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, United States.
5
Department of Medical Physiology, College of Medicine, Texas A&M University Health Science Center, Temple, United States.

Abstract

The application of current channelrhodopsin-based optogenetic tools is limited by the lack of strict ion selectivity and the inability to extend the spectra sensitivity into the near-infrared (NIR) tissue transmissible range. Here we present an NIR-stimulable optogenetic platform (termed 'Opto-CRAC') that selectively and remotely controls Ca(2+) oscillations and Ca(2+)-responsive gene expression to regulate the function of non-excitable cells, including T lymphocytes, macrophages and dendritic cells. When coupled to upconversion nanoparticles, the optogenetic operation window is shifted from the visible range to NIR wavelengths to enable wireless photoactivation of Ca(2+)-dependent signaling and optogenetic modulation of immunoinflammatory responses. In a mouse model of melanoma by using ovalbumin as surrogate tumor antigen, Opto-CRAC has been shown to act as a genetically-encoded 'photoactivatable adjuvant' to improve antigen-specific immune responses to specifically destruct tumor cells. Our study represents a solid step forward towards the goal of achieving remote and wireless control of Ca(2+)-modulated activities with tailored function.

KEYWORDS:

Calcium signaling; Immune response; Nanoparticles; Near infrared; Optogenetics; STIM1; biochemistry; cell biology; human; mouse

PMID:
26646180
PMCID:
PMC4737651
DOI:
10.7554/eLife.10024
[Indexed for MEDLINE]
Free PMC Article

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