Characterization of the shark myelin Po protein.

Myelin, the insulating sheath made by extensive plasma membrane wrapping, is dependent on the presence of highly adhesive molecules that keep the two sides of the membrane in tight contact. The Po glycoprotein (Po) is the major component of the peripheral nervous system (PNS) myelin of mammals. The exact role that Po protein has played in the evolution of myelin is still unclear, but several phylogenetic observations suggest that it is a crucial component in the development of myelin as a multi-lamellar membrane structure. Sharks, which appeared in the fossil record about 400 million years ago, are the first fully myelinated organisms. In this study we investigated the expression pattern of shark myelin Po to suggest a way it might have played a role in the evolution of myelin in the central nervous system. We found that sharks have more than two isoforms (32, 28 and 25 kD), and that some of these might not be fully functional because they lack the domains known for Po homophilic adhesion.

Excess lunatic fringe causes cranial neural crest over-proliferation.

Lunatic fringe is a vertebrate homologue of Drosophila fringe, which plays an important role in modulating Notch signaling. This study examines the distribution of chick lunatic fringe at sites of neural crest formation and explores its possible function by ectopic expression. Shortly after neural tube closure, lunatic fringe is expressed in most of the neural tube, with the exception of the dorsal midline containing presumptive neural crest. Thus, there is a fringe/non-fringe border at the site of neural crest production. Expression of excess lunatic fringe in the cranial neural tube and neural crest by retrovirally mediated gene transfer resulted in a significant increase ( approximately 60%) in the percentage of cranial neural crest cells 1 day after infection. This effect was mediated by an increase in cell division as assayed by BrdU incorporation. Infected embryos had an up-regulation of Delta-1 in the dorsal neural tube and redistribution of Notch-1 to the lumen of the neural tube, confirming that excess fringe modulates Notch signaling. These findings point to a novel role for lunatic fringe in regulating cell division and/or production of neural crest cells by the neural tube.

Myelin-associated glycoprotein, MAG, selectively binds several neuronal proteins.

Myelin-associated glycoprotein (MAG) is a potent inhibitor of axonal regeneration and also, depending on the age and type of neuron, can promote axonal growth. In addition, MAG influences stability of both myelin and the axon in the intact, mature nervous system. The identity of the neuron/axonal MAG-binding receptor responsible for effecting these responses is not known. Here we show that a soluble, chimeric form of MAG, MAG-Fc, can bind to the neuronal cell body and neurites equally well, in a sialic acid-dependent manner. Importantly, MAG-Fc specifically precipitates a number of surface proteins from post-natal cerebellar, dorsal root ganglion (DRG) and PC12 neurons. These proteins are not precipitated by a control Fc-containing chimera and are not apparent when a MAG antibody is included in the precipitation mix as a competitive inhibitor. Based on molecular weight, two prominent proteins of 190 and 250 kD are precipitated from all three neuron types. The 190 kD protein is a sialoglycoprotein, since it is not apparent in the precipitate from neurons which have been desialylated. Other proteins are precipitated but are less abundant and are different for each type of neuron. One or more of these proteins is/are likely to be the functional MAG receptor.

Prior exposure to neurotrophins blocks inhibition of axonal regeneration by MAG and myelin via a cAMP-dependent mechanism.

MAG is a potent inhibitor of axonal regeneration. Here, inhibition by MAG, and myelin in general, is blocked if neurons are exposed to neurotrophins before encountering the inhibitor; priming cerebellar neurons with BDNF or GDNF, but not NGF, or priming DRG neurons with any of these neurotrophins blocks inhibition by MAG/myelin. Dibutyryl cAMP also overcomes inhibition by MAG/myelin, and cAMP is elevated by neurotrophins. A PKA inhibitor present during priming abrogates the block of inhibition. Finally, if neurons are exposed to MAG/myelin and neurotrophins simultaneously, but with the Gi protein inhibitor, inhibition is blocked. We suggest that priming neurons with particular neurotrophins elevates cAMP and activates PKA, which blocks subsequent inhibition of regeneration and that priming is required because MAG/myelin activates a Gi protein, which blocks increases in cAMP. This is important for encouraging axons to regrow in vivo.

Sialoadhesin, myelin-associated glycoprotein and CD22 define a new family of sialic acid-dependent adhesion molecules of the immunoglobulin superfamily.

BACKGROUND: Protein-carbohydrate interactions are believed to be important in many biological processes that involve cell-cell communication. Apart from the selectins, the only well-characterized vertebrate sialic acid-dependent adhesion molecules are CD22 and sialoadhesin; CD22 is a member of the immunoglobulin superfamily that is expressed by B lymphocytes and sialoadhesin is a macrophage receptor. The recent cloning of the gene encoding sialoadhesin has shown that it is also immunoglobulin-like. Both proteins share sequence similarity with the myelin-associated glycoprotein, an adhesion molecule of oligodendrocytes and Schwann cells that has been implicated in the process of myelination, raising the important question of whether myelin-associated glycoprotein is also a sialic acid-binding protein. RESULTS: We have investigated the binding properties of these three receptors when expressed either in monkey COS cells or as chimaeric proteins containing the Fc portion of human immunoglobulin G. We demonstrate that, like sialoadhesin and CD22, myelin-associated glycoprotein mediates cell adhesion by binding to cell-surface glycans that contain sialic acid. We have dissected the specificities of these three adhesins further: whereas sialoadhesin binds equally to the sugar moieties NeuAc alpha 2-->3Gal beta 1-->3(4)GlcNAc or NeuAc alpha 2-->3Gal beta 1-->3GalNAc, myelin-associated glycoprotein recognizes only NeuAc alpha 2-->3Gal beta 1-->3GalNAc and CD22 binds specifically to NeuAc alpha 2-->6Gal beta 1-->4GlcNAc. Furthermore, we show that the recognition of sialylated glycans on the surfaces of particular cell types leads to the selective binding of sialoadhesin to neutrophils, myelin-associated glycoprotein to neurons and CD22 to lymphocytes. CONCLUSIONS: Our findings demonstrate that a subgroup of the immunoglobulin superfamily can mediate diverse biological processes through recognition of specific sialylated glycans on cell surfaces. We propose that this subgroup of proteins be called the sialoadhesin family.

Amino acids and memory consolidation in the cricket. II: Effect of injected amino acids and opioids on memory.

The effect of injections of selected amino acids on memory, given before a maze-learning, was investigated. Thirsty crickets (Pteronemobius sp.) were trained to turn only to one side of a symmetrical Y-shaped maze using reinforcements with water. The insects retained the learned task 24 hr later. N2 anoxia applied immediately after training produced retrograde amnesia. Injections of Ala, Arg, Gln or morphine prior to training blocked the amnesic action of anoxia, whereas those of Cys, Met, Pro, Orn, octopamine or naloxone did not. Naloxone blocked long-term memory formation, but not learning, whereas Pro and Orn blocked both. The antiamnesic effect of morphine and Arg, but not that of Ala, was blocked by naloxone. A hypothesis assigning a neuromodulatory role to some amino acids is put forward.

[Venezuelan equine encephalitis. Review]. / Encefalitis equina venezolana. Revisión.

The Venezuelan equine encephalomyelitis (VEE) is one the most serious viral infections of the nervous system. It has a wide geographic distribution and may give rise to sequela like mental retardation, amnesia, abortion, epilepsy and hidroanencephaly in infected humans and animals. The pathology of this infection is focused mainly in two tissues: lymphohematopoietic and nervous. The VEE virus has a special cytopathic activity on the nervous cells (glia and neurons) while the lesions produced in the myelin are probably a consequence of the immunological response of the host to the infection. The alterations produced by the VEE virus in different neuronal types can originate changes in the brain concentrations of several neurotransmitters and their receptors. Some biochemical modifications that have also been reported could be due to the cytopathic effect of the virus.