The role of under-investigated connexins in musculoskeletal tissue: a brief review with emphasis on bone tissue / El papel de las escasamente investigadas conexinas en el tejido músculo-esquelético: una breve revisión con énfasis en el tejido óseo

Connexins (Cxs) are a family of transmembrane proteins that form gap junctions and hemi-channels, which mediate cell-cell communication between neighboring cells and the respective extracellular milieu in different tissues. Most tissues and cell types throughout the body express one or more Cx proteins, highlighting its importance in regulating cell growth, differentiation, adhesion, migration, cell death and others. Moreover, Cx can propagate intracellular signals through its C-terminus domain, and thus function beyond a mere channel. Cx43 is the most highly expressed and most well studied Cx in bone and musculoskeletal tissues, although Cx40, Cx45, Cx46 and more recently, the Cx37 have been described in bone tissue, along with Cx26, Cx32 and Cx39 in other musculoskeletal tissues. Here, we discuss the basic structure of gap junctions and the role of the Cxs in musculoskeletal tissue, with special focus on Cx37. (AU)

Las conexinas (Cxs) son una familia de proteínas transmembrana que forman uniones en hendidura y hemicanales encargados de mediar la comunicación entre células vecinas y el respectivo medio extracelular en diferentes tejidos. La mayoría de los tejidos y células expresan una o más proteínas conexina, jugando un papel importante en la regulación de la proliferación celular, diferenciación, adhesión, migración y muerte celular, entre otras funciones. Además de actuar como un canal, las conexinas pueden propagar señales intracelulares a través del dominio C-terminal. La Cx43 es la conexina mas expresada y mejor estudiada en el tejido óseo y el músculo, aunque las Cx40, Cx45, Cx46, y mas recientemente Cx37, son también detectadas en el hueso. A su vez la expresión de la Cx26, Cx32 y Cx39 ha sido observada en otros tejidos músculoesqueléticos. En este manuscrito describimos la estructura básica de las uniones tipo gap y el papel que las Cxs, y en especial la Cx37, tienen en tejidos músculo-esqueléticos. (AU)

The distribution of interstitial cells of Cajal in the ileum is not altered by infection with Schistosoma mansoni.

BACKGROUND & OBJECTIVES: The interstitial cells of Cajal (ICC) act as pacemakers that generate slow waves and function as a relay between smooth muscle cells of the gastrointestinal (GI) tract. Recent reports indicate the crucial role played by the ICC in defining GI motility during human disease status like pyloric stenosis, Hirschsprung's disease and ulcerative colitis. Experimental data showed that Nippostrongylus infection in the rat caused an altered GI motility pattern accompanied by a complete loss of ICC-deep muscular plexus. The aim of the present study was to delineate if ICC were similarly affected during Schistosoma mansoni infections, thereby responsible for the disturbed GI motility patterns triggered in the afflicted mammalian host. METHODS & RESULTS: Immunohistochemistry was done using whole mounts and sections from naive and S. mansoni infected mice ileum. Primary antibodies detected Kit-immunoreactivity (Kit-ir representing ICC), PGP-9.5 (protein gene product 9.5 representing a neuronal marker), SK3 (ionic channel marker for non-Kit fibroblast like cells), and Cx43 (gap junction protein representing a muscle marker). Single/double immunofluorescence staining and confocal microscopy depicted that muscle thickness (Cx43-ir) and inflammatory infiltrate increased with infection. Kit-ir ICC and SK3-ir fibroblast like cells (FLC) were present at all normal locations as seen in controls and during acute and chronic stages of infection. INTERPRETATION & CONCLUSION: No disappearance of either ICC population was noted. A preferential (although not exclusive) location of inflammatory infiltrate in contact with SK3-ir FLC in the muscle layer was observed. The present study thus delineated that ICC are not affected during S. mansoni infections, and thereby may not be responsible for mediating the disturbed GI motility patterns caused by schistosomiasis.

Uniones en hendidura y su papel funcional en el tracto reproductor femenino

En el aparato reproductor femenino se expresan diferentes conexinas (Cxs), proteínas que forman canales de uniones en hendidura (CUH) entre células en contacto, permitiendo la coordinación de respuestas metabólicas y/o eléctricas de grupos celulares. Los CUH jugarían un papel relevante en el desarrollo de las células de la granulosa, ya que permiten la comunicación heteróloga entre el ovocito y las células del cúmulo manteniendo la detención meiótica. En la trompa de Falopio, los CUH coordinarían el batido ciliar del epitelio y la contracción muscular, facilitando el desplazamiento de los gametos y del embrión. En el útero, los CUH conectan a las células miometriales y también a las endometriales. El aumento de CUH durante el preparto permitiría la contracción uterina coordinada facilitando el trabajo de parto al término del embarazo. La expresión de las Cxs es regulada por hormonas, lo que explicaría el perfil de CUH presentes en los diversos tipos celulares del tracto genital en diferentes estadios fisiológicos del sistema reproductor.

Molecular signaling in pathogenicity and host recognition in smut fungi taking Karnal bunt as a model system.

Karnal bunt of wheat, incited by a phytopathogen Tilletia indica (Syn. Neovossia indica) is a floret infecting disease. In the floral tissues fungus proliferates and produces massive amount of black spores. In smut fungi, belonging to order Ustilaginales, communication between cells is necessary to regulate growth, differentiation and monokaryotic to dikaryotic transition during pathogenic and sexual development. Neighbouring cells are able to communicate with each other by direct cell to cell contact through plasma membrane bound signaling molecules or through formation of gap junctions and alternatively through secretion of chemical signals if cells are some distance away. Current research efforts toward understanding of pathogenic and sexual development in phytopathogenic fungi, offer a number of opportunities. These include the analysis of molecular signal(s) for direct contribution of sexual interactions to ability of smut and bunt pathogens to cause disease. These efforts will provide not only to explore the mechanisms of pathogenesis, but also to enhance knowledge of basic cellular biology of an economically important group of fungi.

Gap junctions in the cardiovascular and immune systems

Gap junctions are clusters of intercellular channels directly connecting the cytoplasm of adjacent cells. These channels are formed by proteins named connexins and are present in all metazoan organisms where they serve diverse functions ranging from control of cell growth and differentiation to electric conduction in excitable tissues. In this overview we describe the presence of connexins in the cardiovascular and lympho-hematopoietic systems giving the reader a summary of the topics to be covered throughout this edition and a historical perspective of the discovery of gap junctions in the immune system

Gap junctions in cells of the immune system: structure, regulation and possible functional roles

Gap junction channels are sites of cytoplasmic communication between contacting cells. In vertebrates, they consist of protein subunits denoted connexins (Cxs) which are encoded by a gene family. According to their Cx composition, gap junction channels show different gating and permeability properties that define which ions and small molecules permeate them. Differences in Cx primary sequences suggest that channels composed of different Cxs are regulated differentially by intracellular pathways under specific physiological conditions. Functional roles of gap junction channels could be defined by the relative importance of permeant substances, resulting in coordination of electrical and/or metabolic cellular responses. Cells of the native and specific immune systems establish transient homo- and heterocellular contacts at various steps of the immune response. Morphological and functional studies reported during the last three decades have revealed that many intercellular contacts between cells in the immune response present gap junctions or "gap junction-like" structures. Partial characterization of the molecular composition of some of these plasma membrane structures and regulatory mechanisms that control them have been published recently. Studies designed to elucidate their physiological roles suggest that they might permit coordination of cellular events which favor the effective and timely response of the immune system

Gap junction modulation by extracellular signaling molecules: the thymus model

Gap junctions are intercellular channels which connect adjacent cells and allow direct exchange of molecules of low molecular weight between them. Such a communication has been described as fundamental in many systems due to its importance in coordination, proliferation and differentiation. Recently, it has been shown that gap junctional intercellular communication (GJIC) can be modulated by several extracellular soluble factors such as classical hormones, neurotransmitters, interleukins, growth factors and some paracrine substances. Herein, we discuss some aspects of the general modulation of GJIC by extracellular messenger molecules and more particularly the regulation of such communication in the thymus gland. Additionally, we discuss recent data concerning the study of different neuropeptides and hormones in the modulation of GJIC in thymic epithelial cells. We also suggest that the thymus may be viewed as a model to study the modulation of gap junction communication by different extracellular messengers involved in non-classical circuits, since this organ is under bidirectional neuroimmunoendocrine control

Biphasic effects of gap junctional uncoupling agents on the propagation of retinal spreading depression

The spreading depression wave of Leäo (SD) propagates in the nervous tissue at 3-10 mm/min and is a accompanied by an increase of intracellular Ca²+ concentration and a decrease in the extracellular milieu. Recently the spread of Ca²+ waves with propagating velocities of the same order of magnitude has been detected in cultures of nerve cells. It has been suggested that these waves, which can be blocked by gap junctional agents, are related to SD. The present experiments describe some effects of heptanol and octanol (10µM to 10mM), well-known uncoupling agents of gap junctions, on the slow voltage changes and the velocity of propagation of Leäo's phenomenon in isolated chick retina: 1) a 50 to 700 µM concentration of these alcohols in the superfusate solutions increased the velocity, whereas high concentration (1 to 10 mM) decreased and subsequently halted the spread; 2) the recovery period of the slow voltage changes of SD was shorter in the presence of alcohol and its amplitude was larger during faster SD waves. These effects were observed in the retina during successive individual waves as well as in the course of circling SD. All of these effects were reversible, without any sign of damage to the retina. In the concentration range of 50 µM, methanol, ethanol, butanol and cyclo-hexanol had no effect on retinal SD. These data suggest the involvement of gap junctions in Leäo's wave. This involvement is complex and its functional effects together with other factors that influence the velocity of propagation of SD sre being investigated

Junçöes comunicantes no sistema imune: uma alternativa para a comunicaçäo intercelular / Gap junctions in the immune system: an alternative for intercellular communication

Interaçöes celulares complexas säo utilizadas pelo sistema imune para reconhecimento do próprio e näo próprio. A comunicaçäo intercelular por meio de junçöes comunicantes é um dos mecanismos mais básicos de interaçäo celular e pouco se tem estudado sobre este tema no sistema imune. No presente artigo fazemos uma breve descriçäo das proteínas juncionais conhecidas e de suas propriedades. Revisamos também a literatura analisando criticamente os resultados que indicam a presença e possíveis funçöes dessas proteínas no sistema imune