Structure, mechanism and lipid-mediated remodeling of the mammalian Na/H exchanger NHA2.

The Na/H exchanger SLC9B2, also known as NHA2, correlates with the long-sought-after Na/Li exchanger linked to the pathogenesis of diabetes mellitus and essential hypertension in humans. Despite the functional importance of NHA2, structural information and the molecular basis for its ion-exchange mechanism have been lacking. Here we report the cryo-EM structures of bison NHA2 in detergent and in nanodiscs, at 3.

Design of a light-gated proton channel based on the crystal structure of rhodopsin.

The light-driven proton pump rhodopsin (CsR) provides-because of its high expression in heterologous host cells-an opportunity to study active proton transport under controlled electrochemical conditions. In this study, solving crystal structure of CsR at 2.0-Å resolution enabled us to identify distinct features of the membrane protein that determine ion transport directivity and voltage sensitivity.

The rhodopsin-guanylyl cyclase of the aquatic fungus Blastocladiella emersonii enables fast optical control of cGMP signaling.

Blastocladiomycota fungi form motile zoospores that are guided by sensory photoreceptors to areas of optimal light conditions. We showed that the microbial rhodopsin of Blastocladiella emersonii is a rhodopsin-guanylyl cyclase (RhGC), a member of a previously uncharacterized rhodopsin class of light-activated enzymes that generate the second messenger cyclic guanosine monophosphate (cGMP). Upon application of a short light flash, recombinant RhGC converted within 8 ms into a signaling state with blue-shifted absorption from which the dark state recovered within 100 ms.

Photoinduced formation of flavin radicals in BLUF domains lacking the central glutamine.

Blue light receptors using FAD (BLUFs) facilitate blue light-induced signal transduction via light-induced rearrangement of hydrogen bonds between the flavin chromophore and a conserved glutamine side chain. Here, we investigated the photochemistry of the BLUF domain Slr1694 from Synechocystis sp. in which the glutamine side chain was removed.

A photochromic histidine kinase rhodopsin (HKR1) that is bimodally switched by ultraviolet and blue light.

Rhodopsins are light-activated chromoproteins that mediate signaling processes via transducer proteins or promote active or passive ion transport as ion pumps or directly light-activated channels. Here, we provide spectroscopic characterization of a rhodopsin from the Chlamydomonas eyespot. It belongs to a recently discovered but so far uncharacterized family of histidine kinase rhodopsins (HKRs).

Neocortical excitation/inhibition balance in information processing and social dysfunction.

Severe behavioural deficits in psychiatric diseases such as autism and schizophrenia have been hypothesized to arise from elevations in the cellular balance of excitation and inhibition (E/I balance) within neural microcircuitry. This hypothesis could unify diverse streams of pathophysiological and genetic evidence, but has not been susceptible to direct testing. Here we design and use several novel optogenetic tools to causally investigate the cellular E/I balance hypothesis in freely moving mammals, and explore the associated circuit physiology.