Achromatopsia (ACHM) is a congenital cone photoreceptor disorder characterized by impaired color discrimination, low visual acuity, photosensitivity, and nystagmus. To date, six genes have been associated with ACHM (CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, and ATF6), the majority of these being implicated in the cone phototransduction cascade. CNGA3 encodes the CNGA3 subunit of the cyclic nucleotide-gated ion channel in cone photoreceptors and is one of the major disease-associated genes for ACHM. Herein, we provide a comprehensive overview of the CNGA3 variant spectrum in a cohort of 1060 genetically confirmed ACHM patients, 385 (36.3%) of these carrying \"likely disease-causing\" variants in CNGA3. Compiling our own genetic data with those reported in the literature and in public databases, we further extend the CNGA3 variant spectrum to a total of 316 variants, 244 of which we interpreted as \"likely disease-causing\" according to ACMG/AMP criteria. We report 48 novel \"likely disease-causing\" variants, 24 of which are missense substitutions underlining the predominant role of this mutation class in the CNGA3 variant spectrum. In addition, we provide extensive in silico analyses and summarize reported functional data of previously analyzed missense, nonsense and splicing variants to further advance the pathogenicity assessment of the identified variants.

In numerous mammalian species, the nose harbors several compartments populated by chemosensory cells. Among them, the Grueneberg ganglion (GG) located in the anterior nasal region comprises sensory neurons activated by given substances. In rodents, in which the GG has been best studied, these chemical cues mainly include heterocyclic compounds released by predators or by conspecifics. Since some of these substances evoke fear- or stress-associated responses, the GG is considered as a detector for alerting semiochemicals. In fact, certain behavioral and physiological reactions to alarm pheromones and predator-secreted kairomones are attenuated in the absence of a functional GG. Intriguingly, GG neurons are also stimulated by cool temperatures. Moreover, ambient temperatures modulate olfactory responsiveness in the GG, indicating that cross-talks exist between the transduction pathways mediating chemo- and thermosensory signaling in this organ. In this context, exploring the relevant molecular cascades has demonstrated that some chemosensory transduction elements are also crucial for thermosensory signaling in the GG. Finally, for further processing of sensory information, axons of GG neurons project to the olfactory bulb of the brain where they innervate distinct glomerular structures belonging to the enigmatic necklace glomeruli. In this review, the stimuli activating GG neurons as well as the underlying transduction pathways are summarized. Because these stimuli do not exclusively activate GG neurons but also other sensory cells, the biological relevance of the GG is discussed, with a special focus on the role of the GG in detecting alarm signals.

Differences in mating behaviors evolve early during speciation, eventually contributing to reproductive barriers between species. Knowledge of the genetic and genomic basis of these behaviors is therefore integral to a causal understanding of speciation. Acoustic behaviors are often part of the mating ritual in animal species. The temporal rhythms of mating songs are notably species-specific in many vertebrates and arthropods and often underlie assortative mating. Despite discoveries of mutations that disrupt the temporal rhythm of these songs, we know surprisingly little about genes affecting naturally occurring variation in the temporal pattern of singing behavior. In the rapidly speciating Hawaiian cricket genus Laupala, the striking species variation in song rhythms constitutes a behavioral barrier to reproduction between species. Here, we mapped the largest-effect locus underlying interspecific variation in song rhythm between two Laupala species to a narrow genomic region, wherein we find no known candidate genes affecting song temporal rhythm in Drosophila Whole-genome sequencing, gene prediction, and functional annotation of this region reveal an exciting and promising candidate gene, the putative cyclic nucleotide-gated ion channel-like gene, for natural variation in mating behavior. Identification and molecular characterization of the candidate gene reveals a nonsynonymous mutation in a conserved binding domain, suggesting that ion channels are important targets of selection on rhythmic signaling during establishment of behavioral isolation and rapid speciation.

Cyclic nucleotide-modulated channels have important roles in visual signal transduction and pacemaking. Binding of cyclic nucleotides (cAMP/cGMP) elicits diverse functional responses in different channels within the family despite their high sequence and structure homology. The molecular mechanisms responsible for ligand discrimination and gating are unknown due to lack of correspondence between structural information and functional states. Using single particle cryo-electron microscopy and single-channel recording, we assigned functional states to high-resolution structures of SthK, a prokaryotic cyclic nucleotide-gated channel. The structures for apo, cAMP-bound, and cGMP-bound SthK in lipid nanodiscs, correspond to no, moderate, and low single-channel activity, respectively, consistent with the observation that all structures are in resting, closed states. The similarity between apo and ligand-bound structures indicates that ligand-binding domains are strongly coupled to pore and SthK gates in an allosteric, concerted fashion. The different orientations of cAMP and cGMP in the \'resting\' and \'activated\' structures suggest a mechanism for ligand discrimination.

Apple ring rot caused by the fungus Botryosphaeria dothidea is one of the devastating diseases. Up to date, the responsive mechanism of apple plant to this disease remains unclear. In the present study, an apple CNGC gene (designated as MdCNGC1) was found among highly expressed genes responding to B. dothidea infection. The expression of MdCNGC1 was different among apple cultivars with different resistance to B. dothidea. Intriguingly, MdCNGC1 expression was not induced by other two apple pathogens, Marssonina coronaria and Valsa ceratosperma. Ectopic overexpression of MdCNGC1 in Nicotiana benthamiana conferred elevated susceptibility to bacterial and fungal pathogens. Notably, overexpression of MdCNGC1 reduced salicylic acid (SA) accumulation induced by Alternaria alternata or Pseudomonas syringae. Decreased induction of pathogenesis-related (PR) genes and ROS accumulation were also observed in MdCNGC1-overexpressing plants. Up-regulated scavenging systems as indicated by enhanced expressions of CAT, APX, SOD genes and activities of antioxidative enzymes may in part contribute to reduced ROS accumulation. MdCNGC1 expression in N. benthamiana also decreased flg22 and chitosan-induced callose deposition and lowered the expression of NbPMR4, an ortholog of Arabidopsis callose synthase gene PMR4. These combined results suggested that MdCNGC1 might be a negative factor to plant resistance to bacterial and fungal pathogens.

The Arabidopsis autoimmune mutant, defense-no death 1 (dnd1) is a null mutant of CYCLIC NUCLEOTIDE-GATED ION CHANNEL2 (AtCNGC2). dnd1 exhibits constitutive pathogen resistance responses including higher levels of endogenous salicylic acid (SA), which is an important signaling molecule for pathogen defense responses. Recently we have reported that dnd1 exhibits a significantly delayed flowering phenotype, indicating the involvement of AtCNGC2 in flowering transition. However, since SA has been known to influence flowering timing as a positive regulator, the delayed flowering phenotype in dnd1 was unexpected. In this study, we have asked whether SA is involved in the dnd1-mediated delayed flowering phenotype. In addition, in order to gain insight into the involvement of SA and CNGCs in flowering transition, we analyzed the flowering transition of cpr22, another CNGC mutant with a similar autoimmune phenotype as dnd1 (including high SA accumulation), and null mutants of several other CNGCs. Our data suggest that dnd1 does not require SA or SA signaling for its delayed flowering phenotype, while SA was responsible for the early flowering phenotype of cpr22. None of the other CNGC mutants besides AtCNGC4 (1) displayed an alteration in flowering transition. This indicates that AtCNGC2 and AtCNGC4 have a unique role controlling flowering timing and this function is independent from its role in pathogen defense.

Plants sense and transmit nutrient-deprivation signals to the nucleus. This increasingly interesting research field advances knowledge of signal transduction pathways for mineral deficiencies. The understanding of this topic for most micronutrients, especially boron (B), is more limited. Several hypotheses have been proposed to explain how a B deprivation signal would be conveyed to the nucleus, which are briefly summarized in this review. These hypotheses do not explain how so many metabolic and physiological processes quickly respond to B deficiency. Short-term B deficiency affects the cytosolic Ca(2+) levels as well as root expression of genes involved in Ca(2+) signaling. We propose and discuss that Ca(2+) and Ca(2+)-related proteins - channels/transporters, sensor relays, and sensor responders - might have major roles as intermediates in a transduction pathway triggered by B deprivation. This hypothesis may explain how plants sense and convey the B-deprivation signal to the nucleus and modulate physiological responses. The possible role of arabinogalactan-proteins in the B deficiency signaling pathway is also taken into account.

Over the last decade a substantial number of lesion mimic mutants (LMM) have been isolated and a growing number of the genes have been cloned. It is now becoming clear that these mutants are valuable tools to dissect various aspects of programmed cell death (PCD) and pathogen resistance pathways in plants. Together with other forward genetics approaches LMMs shed light on the PCD machinery in plant cells and revealed important roles for sphingolipids, Ca(2+) and chloroplast-derived porphyrin-metabolites during cell death development.