title: Near-infrared photoactivatable control of Ca(2+) signaling and optogenetic immunomodulation.
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.
authors.affiliation: Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, United States.
authors.forename: Lian
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States.
authors.forename: Yuanwei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, United States.
authors.forename: Guolin
authors.initials: G
authors.lastname: Ma
authors.affiliation: Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, United States.
authors.forename: Peng
authors.initials: P
authors.lastname: Tan
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States.
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, United States.
authors.forename: Shengbing
authors.initials: S
authors.lastname: Zang
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wu
authors.affiliation: Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, United States.
authors.forename: Ji
authors.initials: J
authors.lastname: Jing
authors.affiliation: Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, United States.
authors.forename: Shaohai
authors.initials: S
authors.lastname: Fang
authors.affiliation: Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, China.
authors.forename: Youjun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, United States.
authors.forename: Yun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, United States.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Hogan
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States.
authors.forename: Gang
authors.initials: G
authors.lastname: Han
authors.affiliation: Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, United States.|Department of Medical Physiology, College of Medicine, Texas A&M University Health Science Center, Temple, United States.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000528:radiation effects*; D003713:Dendritic Cells / Q000502:physiology / Q000528:radiation effects; D004195:Disease Models, Animal; D056747:Immunomodulation; D007259:Infrared Rays; D008264:Macrophages / Q000502:physiology / Q000528:radiation effects; D008545:Melanoma / Q000276:immunology / Q000628:therapy; D051379:Mice; D062308:Optogenetics / Q000379:methods*; D013601:T-Lymphocytes / Q000502:physiology / Q000528:radiation effects
keywords: Calcium signaling; Immune response; Nanoparticles; Near infrared; Optogenetics; STIM1; biochemistry; cell biology; human; mouse