TY  - JOUR
A1  - Hegemann, Peter
A1  - Nagel, Georg
T1  - From channelrhodopsins to optogenetics
JF  - EMBO Molecular Medicine
N2  - We did not expect that research on the molecular mechanism of algal phototaxis or archaeal light‐driven ion transport might interest readers of a medical journal when we conceived and performed our experiments a decade ago. On the other hand, it did not escape our attention that channelrhodopsin is helping an ever‐increasing number of researchers to address their specific questions. For example, the channelrhodopsin approach is used to study the molecular events during the induction of synaptic plasticity or to map long‐range connections from one side of the brain to the other, and to map the spatial location of inputs on the dendritic tree of individual neurons. The current applications have been summarized in a number of recent reviews (Fenno et al, 2011; Yizhar et al, 2011; Zhang et al, 2011). Here, we give personal insight into the history of the discovery of channelrhodopsin and a biophysical perspective on this remarkable class of proteins that has been the main topic of our research since the 1990s.
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129036
VL  - 5
IS  - 2
ER  - 
TY  - JOUR
A1  - Scheib, Ulrike
A1  - Broser, Matthias
A1  - Constantin, Oana M.
A1  - Yang, Shang
A1  - Gao, Shiqiang
A1  - Mukherjee, Shatanik
A1  - Stehfest, Katja
A1  - Nagel, Georg
A1  - Gee, Christine E.
A1  - Hegemann, Peter
T1  - Rhodopsin-cyclases for photocontrol of cGMP/cAMP and 2.3 Å structure of the adenylyl cyclase domain
JF  - Nature Communications
N2  - The cyclic nucleotides cAMP and cGMP are important second messengers that orchestrate fundamental cellular responses. Here, we present the characterization of the rhodopsinguanylyl cyclase from Catenaria anguillulae (CaRhGC), which produces cGMP in response to green light with a light to dark activity ratio > 1000. After light excitation the putative signaling state forms with tau = 31 ms and decays with tau = 570 ms. Mutations (up to 6) within the nucleotide binding site generate rhodopsin-adenylyl cyclases (CaRhACs) of which the double mutated YFP-CaRhAC (E497K/C566D) is the most suitable for rapid cAMP production in neurons. Furthermore, the crystal structure of the ligand-bound AC domain (2.25 angstrom) reveals detailed information about the nucleotide binding mode within this recently discovered class of enzyme rhodopsin. Both YFP-CaRhGC and YFP-CaRhAC are favorable optogenetic tools for non-invasive, cell-selective, and spatio-temporally precise modulation of cAMP/cGMP with light.
KW  - Enzymes
KW  - Molecular biophysics
KW  - Molecular neuroscience
KW  - X-ray crystallography
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228517
VL  - 9
ER  -