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1

Signalling: basics and evolution.

100%

Williams R. J. P.

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vol. 51

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issue 2

281-298

EN

Signalling concerns the transfer of information from one body, a source, to another, a receiver in order to stimulate activity. The problem arises with the word information. It is defined as what is transferred in a sequence of things, say between people, e.g. words or signs. The idea of signalling between people is then obvious but it is not clear in cell biology. Information transfer, signalling, is required for the organisation of all cellular activity but we must ask what is transferred and how is it transmitted and received? Sometimes it is assumed that all information, i.e. organisation in a cell, is represented in the DNA sequence. This is incorrect. We shall show that the environment is a second source of information concerning material and energy. The receiving party from both DNA and the environment is general metabolism. The metabolism then signals back and sends information to both DNA and uptake from the environment. Even then energy is needed with machinery to send out all signals. This paper examines the way signalling evolved from prokaryotes through to man. In this process the environmental information received increased to the extent that finally the brain is a phenotypic as much as a genotypic organ within a whole organism. By phenotypic we mean it is organised by and interactive with information from the environment.

2

The ancestry and cumulative evolution of immune reactions

67%

Dzik J. M.

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2010

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vol. 57

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issue 4

443-466

EN

The last two decades of study enriched greatly our knowledge of how the immune system originated and the sophisticated immune mechanisms of today's vertebrates and invertebrates developed. Even unicellular organisms possess mechanisms for pathogen destruction and self recognition. The ability to distinguish self from non-self is a prerequisite for recognition of sexual compatibility and ensuring survival. Molecules involved in these processes resemble those found in the phagocytic cells of higher organisms. Recognition of bacteria by scavenger receptors induces phagocytosis or endocytosis. The phagocytic mechanisms characterizing the amoeboid protozoans developed further during the evolution towards innate immunity. The scavenger receptor cysteine-rich domain SRCR is encoded in the genomes from the most primitive sponges to mammals. The immune system of sponges comprises signal transduction molecules which occur in higher metazoans as well. Sponges already possess recognition systems for pathogenic bacteria and fungi, based on membrane receptors (a lipopolysaccharide-interacting protein, a cell surface receptor recognizing β(1 → 3)-d-glucans of fungi). Perforin-like molecules and lysozymes are involved, among others, in defense in sponges. Reactive oxygen and nitrogen species function in the immunity of early metazoan. Genes encoding the family of reactive oxygen-generating NADPH oxidases (Noxes) are found in a variety of protists and plants. The NO synthases of cnidarians, mollusks, and chordates are conserved with respect to the mammalian NOS. The antimicrobial peptides of protozoans, amoebapores, are structural and functional analogs of the natural killer cell peptide, NK-lysin, of vertebrates. An ancestral S-type lectin has been found in sponges. Opsonizing properties of lectins and the ability to agglutinate cells justify their classification as primitive recognition molecules. Invertebrate cytokines are not homologous to those of vertebrate, and their functional convergence was presumably enabled by the general similarity of the lectin-like recognition domain three-dimensional structure. Sponges contain molecules with SCR/CCP domains that show high homology to the mammalian regulators of complement activation (RCA family). A multi-component complement system comprising at least the central molecule of the complement system, C3, Factor B, and MASP developed in the cnidarians and evolved into the multilevel cascade engaged in innate and acquired immunity of vertebrates. The adaptive immune system of mammals is also deeply rooted in the metazoan evolution. Some its precursors have been traced as deep as in sponges, namely, two classes of receptors that comprise Ig-like domains, the receptor tyrosine kinases (RTK), and the non-enzymic sponge adhesion molecules (SAM). The antibody-based immune system defined by the presence of the major histocompatibility complex (MHC), T-cell receptor (TCR), B-cell receptor (BCR) or recombination activating genes (RAGs) is known beginning from jawed fishes. However, genes closely resembling RAG1 and RAG2 have been uncovered in the genome of a see urchin. The ancestry of MHC gene remains unknown. Similarly, no homologue of the protein binding domain (PBD) in MHC molecules has been found in invertebrates. The pathway by which endogenous peptides are degraded for presentation with class I MHC molecules utilizes mechanisms similar to those involved in the normal turnover of intracellular proteins, apparently recruited to work also for the immune system. Several cDNAs coding for lysosomal enzymes, e.g., cathepsin, have been isolated from sponges. All chromosomal duplication events in the MHC region occurred after the origin of the agnathans but before the gnathostomes split from them. The V-domains of the subtype found in the receptors of T and B-cells are known from both agnathans and cephalochordates, although they do not rearrange. The rearrangement mechanism of the lymphocyte V-domains suggests its origin from a common ancestral domain existing before the divergence of the extant gnathostome classes. Activation-induced deaminase (AID) - homologous proteins have been found only in the gnathostomes. It appears thus that the adaptive immunity of vertebrates is a result of stepwise accumulation of small changes in molecules, cells and organs over almost half a billion years.

3

Melatonina, wielofunkcyjna cząsteczka sygnałowa w organizmie ssaka: miejsca biosyntezy, funkcje, mechanizmy działania

67%

Skwarło-Sońta K., Majewski P.

Folia Medica Lodziensia

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2010

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vol. 37

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issue 1

15-55

EN

Methoxyindole hormone - melatonin (MEL) is produced and released by the mammalian pineal gland in a circadian rhythm exhibiting a low level during the day and an elevation at night, strictly dependent on the environmental lighting conditions. The main MEL function is, therefore, to synchronize diurnal rhythms of several physiological processes and for the diurnally active species (including humans) it gives information on the beginning of sleepiness. For the nocturnal species, however, elevated MEL level serves as a signal to start locomotor and feeding activity. In seasonal breeders the pineal gland function synchronizes the time of gonadal development and sexual activity with the external conditions in a way that progeny appears in the optimal climatic moment. MEL is produced also extrapineally, e.g. in the gastro-intestinal tract and bone marrow, where it exerts a protective effect due to its activity as an antioxidant and a potent free radical scavenger. Being both lipid and water soluble, MEL is able to cross biological barriers and, therefore, it uses several cellular mechanism to exert its physiological activity, including membrane and nuclear receptors, proteins of the cytoskeleton, mitochondrial membrane stabilization. MEL is also involved in immunomodulation, the effects are different and dependent on numerous factors, nevertheless, its immunostimulatory activity is generally well accepted. Additionally, activated immune cells are able to produce MEL acting in an auto- and paracrine way. As an efficient antioxidant MEL exerts the anti-inflammatory effect, which, reciprocally, modulates the pineal gland biosynthetic activity adapting it to temporary endogenous conditions.

PL

Szyszynka ssaków produkuje i wydziela do krwi melatoninę (MEL) w rytmie dobowym, którego cechą charakterystyczną jest wysoki poziom w nocy niski w dzień, a czas nocnej syntezy zaleŜy od warunków świetlnych otoczenia. Dzięki temu MEL synchronizuje wiele procesów fizjologicznych przebiegających rytmicznie, a jako chemiczny sygnał ciemności przekazuje gatunkom o aktywności dziennej (w tym ludziom) informację o rozpoczęciu pory snu. Gatunki aktywne w nocy inaczej interpretują sygnał melatoninowy. Dla zwierząt rozmnaŜających się sezonowo informacja niesiona przez MEL stanowi sygnał do takiej synchronizacji funkcji rozrodczych z warunkami klimatycznymi, aby potomstwo mogło pojawić się w optymalnym momencie. Melatonina powstaje takŜe pozaszyszynkowo, np. w układzie pokarmowym, gdzie pełni funkcje ochronne, związane z aktywnym zmiataniem wolnych rodników i właściwościami antyoksydacyjnymi. Jako cząsteczka amfifilowa moŜe przekraczać bariery biologiczne, dlatego swoje efekty moŜe wywierać za pośrednictwem wielu róŜnych mechanizmów takich jak: wiązanie z receptorami błonowymi i jądrowymi, białkami cytozolowymi, stabilizowanie błony mitochondrialnej. MEL wykazuje działanie immunomodulacyjne, zaleŜne od wielu czynników, choć zasadniczo wydaje się być czynnikiem wspomagającym odporność, a aktywowane komórki odpornościowe takŜe syntetyzują MEL działającą auto- i parakrynowo. Dzięki właściwościom antyoksydacyjnym pełni istotną rolę przeciwzapalną, z kolei toczący się proces zapalny moduluje aktywność biosyntetyczną szyszynki, dostosowując je do aktualnych warunków w organizmie.

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2 Acta Biochimica Polonica

1 Folia Medica Lodziensia

2 2010

1 2004

1 Dzik J. M.

1 Majewski P.

1 Skwarło-Sońta K.

1 Williams R. J. P.

Signalling: basics and evolution.

The ancestry and cumulative evolution of immune reactions

Melatonina, wielofunkcyjna cząsteczka sygnałowa w organizmie ssaka: miejsca biosyntezy, funkcje, mechanizmy działania