Yuri V. Panchin

Evolution of gap junction proteins--the pannexin alternative.

SUMMARY Gap junctions provide one of the most common forms of intercellular communication. They are composed of membrane proteins that form a channel that is permeable to ions and small molecules, connecting the cytoplasm of adjacent cells. Gap junctions serve similar functions in all multicellular animals (Metazoa). Two unrelated protein families are involved in this function; connexins, which are found only in chordates, and pannexins, which are ubiquitous and present in both chordate and invertebrate genomes. The involvement of mammalian pannexins to gap junction formation was recently confirmed. Now it is necessary to consider the role of pannexins as an alternative to connexins in vertebrate intercellular communication.

Expression of pannexin family of proteins in the retina

Expression of the Panx1 and Panx2 members of the pannexin family of gap junction proteins was studied in the retina by in situ hybridization and qRT‐PCR. Both pannexins showed robust expression across the retina with predominant accumulation in the retinal ganglion cells (RGCs). In concordance, immunohistochemical analysis showed accumulation of the Panx1 protein in RGCs, amacrine, horizontal cells and their processes. Two Panx1 isoforms were detected: a ubiquitously expressed 58 kDa protein, and a 43 kDa isoform that specifically accumulated in the retina and brain. Our results indicated that Panx1 and Panx2 are abundantly expressed in the retina, and may therefore contribute to the electrical and metabolic coupling, or to signaling between retinal neurons via the secondary messengers.

What is hidden in the pannexin treasure trove: the sneak peek and the guesswork

Connexins had been considered to be the only class of the vertebrate proteins capable of gap junction formation; however, new candidates for this function with no homology to connexins, termed pannexins were discovered. So far three pannexins were described in rodent and human genomes: Panx1, Panx2 and Panx3. Expressions of pannexins can be detected in numerous brain structures, and now found both in neuronal and glial cells. Hypothetical roles of pannexins in the nervous system include participating in sensory processing, hippocampal plasticity, synchronization between hippocampus and cortex, and propagation of the calcium waves supported by glial cells, which help maintain and modulate neuronal metabolism. Pannexin also may participate in pathological reactions of the neural cells, including their damage after ischemia and subsequent cell death. Recent study revealed non‐gap junction function of Panx1 hemichannels in erythrocytes, where they serve as the conduits for the ATP release in response to the osmotic stress. High‐throughput studies produced some evidences of the pannexin involvement in the process of tumorigenesis. According to brain cancer gene expression database REMBRANDT, PANX2 expression levels can predict post diagnosis survival for patients with glial tumors. Further investigations are needed to verify or reject hypotheses listed.

The origin of Metazoa: a transition from temporal to spatial cell differentiation†

For over a century, Haeckels Gastraea theory remained a dominant theory to explain the origin of multicellular animals. According to this theory, the animal ancestor was a blastula‐like colony of uniform cells that gradually evolved cell differentiation. Today, however, genes that typically control metazoan development, cell differentiation, cell‐to‐cell adhesion, and cell‐to‐matrix adhesion are found in various unicellular relatives of the Metazoa, which suggests the origin of the genetic programs of cell differentiation and adhesion in the root of the Opisthokonta. Multicellular stages occurring in the complex life cycles of opisthokont protists (mesomycetozoeans and choanoflagellates) never resemble a blastula. Here, we discuss a more realistic scenario of transition to multicellularity through integration of pre‐existing transient cell types into the body of an early metazoon, which possessed a complex life cycle with a differentiated sedentary filter‐feeding trophic stage and a non‐feeding blastula‐like larva, the synzoospore. Choanoflagellates are considered as forms with secondarily simplified life cycles.

New words in human mutagenesis

BackgroundThe substitution rates within different nucleotide contexts are subject to varying levels of bias. The most well known example of such bias is the excess of C to T (C > T) mutations in CpG (CG) dinucleotides. The molecular mechanisms underlying this bias are important factors in human genome evolution and cancer development. The discovery of other nucleotide contexts that have profound effects on substitution rates can improve our understanding of how mutations are acquired, and why mutation hotspots exist.ResultsWe compared rates of inherited mutations in 1-4 bp nucleotide contexts using reconstructed ancestral states of human single nucleotide polymorphisms (SNPs) from intergenic regions. Chimp and orangutan genomic sequences were used as outgroups. We uncovered 3.5 and 3.3-fold excesses of T > C mutations in the second position of ATTG and ATAG words, respectively, and a 3.4-fold excess of A > C mutations in the first position of the ACAA word.ConclusionsAlthough all the observed biases are less pronounced than the 5.1-fold excess of C > T mutations in CG dinucleotides, the three 4 bp mutation contexts mentioned above (and their complementary contexts) are well distinguished from all other mutation contexts. This provides a challenge to discover the underlying mechanisms responsible for the observed excesses of mutations.

Endothelial function is impaired in conduit arteries of pannexin1 knockout mice

Pannexin1 is ubiquitously expressed in vertebrate tissues, but the role it plays in vascular tone regulation remains unclear. We found that Pannexin1 expression level is much higher in the endothelium relative to smooth muscle of saphenous artery. The ability of endothelium-intact arteries for dilation was significantly impaired whereas contractile responses were considerably increased in mice with genetic ablation of Pannexin1. No such increased contractile responses were detected in the endothelium-denuded arteries. Combined, our findings suggest a new function of Pannexin1 as an important player in normal endothelium-dependent regulation of arterial tone, where it facilitates vessel dilation and attenuates constriction.Reviewed by Dr. Armen Mulkidjanian and Dr. Alexander Lobkovsky.

Effects of acetylcholine and glutamate on isolated neurons of locomotory network of Clione

IN Clione limacina, locomotory rhythm is produced in the central pattern generator by reciprocal activity of two groups of interneurons. Dorsal (D) and ventral (V) phase interneurons activate neurons of the same phase and inhibit neurons of the opposite phase. Which neurotransmitters are used by these interneurons is not clear. In this study, identified follower neurons to V and D interneurons were isolated, and their responses to the local application of potential neurotransmitters were examined. Acetylcholine exerted inhibitory action on the isolated D-phase neurons and excitatory action on V-phase neurons. Glutamate produced excitation in D-phase neurons, and inhibition in V-phase neurons. These results suggest that acetylcholine is the neurotransmitter of D-phase interneurons, while glutamate might be the neurotransmitter of V-phase interneurons.

EXCLUSIVE SEQUENCES OF DIFFERENT GENOMES

We studied the distribution of 1-7 bp words in a dataset that includes 139 complete eukaryotic genomes, 33 masked eukaryotic genomes and coding regions from 35 genomes. We tested different statistical models to determine over- and under-represented words. The method described by Karlin et al. has the strongest predictive power compared to other methods. Using this method we identified over- and under-represented words consistent within a large array of taxonomic groups. Some of those words have not yet been described as exclusive. For example, CGCG is over-represented in CG-deficient organisms. We also describe exceptions for widely known exclusive words, such as CG and TA.

Cellular mechanism for the temperature sensitive spatial orientation in Clione

THE swimming mollusk Clione is normally oriented vertically. As water is warmed, this orientation is lost or reversed. CPB3 interneurons, which transmit signals from the statocyst receptors (SRCs) to the tail motoneurons and play a key role in space orientation, were strongly depolarized upon warming. Normally, intracellular stimulation of the rostro-dorsal SRC (DSRC) excited CPB3b. Upon warming the excitation gradually decreased and in some cases was even replaced by inhibition. The reversal potential for the synaptic potentials (PSP) produced in CPB3b by DSRC stimulation is depolarized relative to the normal membrane potential at lower temperature. Warming causes depolarization of the membrane potential such that the PSP reversal potential is approached and even passed, with attenuant effects on PSP amplitude and polarity. This effect provides a mechanism for the temperature sensitive changes in the orientation of Clione.

Midichlorians - the biomeme hypothesis: is there a microbial component to religious rituals?

BackgroundCutting edge research of human microbiome diversity has led to the development of the microbiome-gut-brain axis concept, based on the idea that gut microbes may have an impact on the behavior of their human hosts. Many examples of behavior-altering parasites are known to affect members of the animal kingdom. Some prominent examples include Ophiocordyceps unilateralis (fungi), Toxoplasma gondii (protista), Wolbachia (bacteria), Glyptapanteles sp. (arthropoda), Spinochordodes tellinii (nematomorpha) and Dicrocoelium dendriticum (flat worm). These organisms belong to a very diverse set of taxonomic groups suggesting that the phenomena of parasitic host control might be more common in nature than currently established and possibly overlooked in humans.Presentation of the hypothesisSome microorganisms would gain an evolutionary advantage by encouraging human hosts to perform certain rituals that favor microbial transmission. We hypothesize that certain aspects of religious behavior observed in the human society could be influenced by microbial host control and that the transmission of some religious rituals could be regarded as the simultaneous transmission of both ideas (memes) and parasitic organisms.Testing the hypothesisWe predict that next-generation microbiome sequencing of samples obtained from gut or brain tissues of control subjects and subjects with a history of voluntary active participation in certain religious rituals that promote microbial transmission will lead to the discovery of microbes, whose presence has a consistent and positive association with religious behavior. Our hypothesis also predicts a decline of participation in religious rituals in societies with improved sanitation.Implications of the hypothesisIf proven true, our hypothesis may provide insights on the origin and pervasiveness of certain religious practices and provide an alternative explanation for recently published positive associations between parasite-stress and religiosity. The discovery of novel microorganisms that affect host behavior may improve our understanding of neurobiology and neurochemistry, while the diversity of such organisms may be of interest to evolutionary biologists and religious scholars.ReviewersThis article was reviewed by Prof. Dan Graur, Dr. Rob Knight and Dr. Eugene Koonin