Differential galactosylation of neuronal and haematopoietic signal regulatory protein-(α) determines its cellular binding-specificity

2001 ◽  
Vol 114 (7) ◽  
pp. 1321-1329 ◽  
Author(s):  
IM van Den Nieuwenhof ◽  
C. Renardel De Lavalette ◽  
N. Diaz ◽  
I. van Die ◽  
TK van Den Berg
Keyword(s):  
Regulatory Protein ◽  
Binding Specificity ◽  
Cellular Interactions ◽  
Binding Studies ◽  
Cerebellar Neurons ◽  
Tissue Specific ◽  
Functional Interactions ◽  
Ig Superfamily ◽  
The Brain

Signal regulatory protein-(α) (SIRP(α)) is a member of the Ig superfamily selectively expressed by neuronal and myeloid cells. The molecule mediates functional interactions with CD47/integrin-associated protein. Here we provide evidence for the tissue-specific glycosylation of neuronal and haematopoietic SIRP(α). We demonstrate a major difference in the galactosylation of N-linked glycans isolated from neuronal (i.e. brain-derived) SIRP(α) as compared to myeloid (i.e. spleen-derived) SIRP(α), with neuronal SIRP(α) almost completely lacking galactose. (β)4-galactosyltransferase assays demonstrated that this is most likely due to a low galactosylation capacity of the brain. In order to investigate the role of galactosylation of SIRP(α) in cellular interactions, soluble recombinant SIRP(α) glycoforms containing galactose (SIRP(α)-Fc) or lacking galactose (SIRP(α)((Δ)Gal)-Fc) were produced. Binding studies demonstrated superior binding of SIRP(α)((Δ)Gal)-Fc to cerebellar neurons and isolated lymphocytes. In contrast, SIRP(α)-Fc bound relatively strong to macrophages. These data show that the galactosylation of SIRP(α) determines its cellular binding specificity.

scholarly journals Heterotopic ossification after central nervous system injuries: understanding of pathogenesis

2018 ◽  
Vol 25 (3-4) ◽  
pp. 119-124
Author(s):  
I. F Gareev ◽  
O. A Beylerli ◽  
A. K Vakhitov
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Heterotopic Ossification ◽  
Genetic Factors ◽  
Cellular Interactions ◽  
Heterotopic Ossifications ◽  
The Brain

Available data on the pathogenesis, cellular interactions, role of inflammation, humoral and genetic factors in the formation of heterotopic ossifications resulting from injuries of the brain or spinal cord are presented.

scholarly journals THE TIMING OF PUBERTY: WELL-KNOWN AND NEW ISSUES

2013 ◽  
Vol 19 (3) ◽  
pp. 227-236 ◽  
Author(s):  
I. L. Nikitina
Keyword(s):  
Population Based ◽  
Reproductive Capacity ◽  
Cellular Interactions ◽  
Metabolic Hormones ◽  
Neuronal Communication ◽  
Sexual Characteristics ◽  
Brain Sexual Differentiation ◽  
Timing Of Puberty ◽  
The Brain

Puberty is an important developmental milestone. It can be considered as a complex sequence of biological  events leading to progressive maturation of sexual characteristics ultimately leading to attainment of full  reproductive capacity. The decline in age at puberty in the general population has been paralleled by an increase  in the number of girls referred for evaluation of precocious puberty (PP). The recent pubertal trends have resulted in a concomitant lowering of the lower limit of normality of the pubertal onset. However, evidence suggests that  age at the gonadotropin and sex steroid surges have not changed. Thus, it looks as if an increasing proportion of  contemporary early pubertal girls may experience isolated gonadotropinindependent thelarche rather than central  PP, which may not be discernible on pubertal examination alone. Thus, the population-based limits of normality  srapid progressive PP as well as intracranial and other underlying pathology. The initiation of mammalian puberty  requires an increased pulsatile release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. This  increase is brought about by changes in transsynaptic and glial-neuronal communication. Coordination of these  cellular interactions likely requires the participation of sets of genes hierarchically arranged within functionally  connected networks. The role of kisspeptins in the control of GnRH neurons and the transmission of the regulatory  actions of key signals, such as sex steroids, metabolic hormones and environmental cues, has been recently  studied, point out that the Kiss1 system is an indispensable player of the brain sexual differentiation during early  periods of maturation and the timing of puberty onset.

scholarly journals Microglial SIRPα regulates the emergence of CD11c+ microglia and demyelination damage in white matter

2018 ◽  
Author(s):  
Miho Sato-Hashimoto ◽  
Tomomi Nozu ◽  
Riho Toriba ◽  
Ayano Horikoshi ◽  
Miho Akaike ◽  
...  
Keyword(s):  
White Matter ◽  
Membrane Protein ◽  
Functional Role ◽  
Regulatory Protein ◽  
Genetic Ablation ◽  
Brain White Matter ◽  
Expression Of Genes ◽  
The Brain ◽  
Repair Phase

AbstractA characteristic subset of microglia expressing CD11c appears in response to brain damage. However, the functional role of CD11c+ microglia, as well as the mechanism of its induction, are poorly understood. Here we report that the genetic ablation of signal regulatory protein α (SIRPα), a membrane protein, induced CD11c+ microglia in the brain white matter. Mice lacking CD47, a physiological ligand of SIRPα, and microglia-specific SIRPα knockout mice exhibited the same phenotype, suggesting the interaction between microglial SIRPα and CD47 on neighbouring cells suppressed the emergence of CD11c+ microglia. A lack of SIRPα did not cause detectable damage in the white matter, but resulted in the increased expression of genes characteristic of the repair phase after demyelination. In addition, cuprizone-induced demyelination was alleviated by the microglia-specific ablation of SIRPα. Thus, microglial SIRPα suppresses the induction of CD11c+ microglia that have the potential to accelerate the repair of damaged white matter.

scholarly journals CD47 in the Brain and Neurodegeneration: An Update on the Role in Neuroinflammatory Pathways

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3943
Author(s):  
Seyed Mohammad Gheibihayat ◽  
Ricardo Cabezas ◽  
Nikita G. Nikiforov ◽  
Tannaz Jamialahmadi ◽  
Thomas P. Johnston ◽  
...  
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Myeloid Leukemia ◽  
Therapeutic Potential ◽  
Lymphoblastic Leukemia ◽  
Tyrosine Phosphatase ◽  
Cell Receptor ◽  
Sh2 Domain ◽  
Ig Superfamily ◽  
The Brain

CD47 is a receptor belonging to the immunoglobulin (Ig) superfamily and broadly expressed on cell membranes. Through interactions with ligands such as SIRPα, TSP-1, integrins, and SH2-domain bearing protein tyrosine phosphatase substrate-1 (SHPS-1), CD47 regulates numerous functions like cell adhesion, proliferation, apoptosis, migration, homeostasis, and the immune system. In this aspect, previous research has shown that CD47 modulates phagocytosis via macrophages, the transmigration of neutrophils, and the activation of T-cells, dendritic cells, and B-cells. Moreover, several studies have reported the increased expression of the CD47 receptor in a variety of diseases, including acute lymphoblastic leukemia (ALL), chronic myeloid leukemia, non-Hodgkin’s lymphoma (NHL), multiple myeloma (MM), bladder cancer, acute myeloid leukemia (AML), Gaucher disease, Multiple Sclerosis and stroke among others. The ubiquitous expression of the CD47 cell receptor on most resident cells of the CNS has previously been established through different methodologies. However, there is little information concerning its precise functions in the development of different neurodegenerative pathologies in the CNS. Consequently, further research pertaining to the specific functions and roles of CD47 and SIRP is required prior to its exploitation as a druggable approach for the targeting of various neurodegenerative diseases that affect the human population. The present review attempts to summarize the role of both CD47 and SIRP and their therapeutic potential in neurodegenerative disorders.

scholarly journals C/EBPβIsoforms Expression in the Rat Brain during the Estrous Cycle

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Valeria Hansberg-Pastor ◽  
Ana Gabriela Piña-Medina ◽  
Aliesha González-Arenas ◽  
Ignacio Camacho-Arroyo
Keyword(s):  
Rat Brain ◽  
Estrous Cycle ◽  
Brain Areas ◽  
Tissue Specific ◽  
Sex Steroid Hormone ◽  
Female Sex Hormones ◽  
Enhancer Binding Protein ◽  
Differentiation And Proliferation ◽  
The Brain

The CCAAT/enhancer-binding protein beta (C/EBPβ) is a transcription factor expressed in different areas of the brain that regulates the expression of several genes involved in cell differentiation and proliferation. This protein has three isoforms (LAP1, LAP2, and LIP) with different transcription activation potential. The role of female sex hormones in the expression pattern of C/EBPβisoforms in the rat brain has not yet been described. In this study we demonstrate by western blot that the expression of the three C/EBPβisoforms changes in different brain areas during the estrous cycle. In the cerebellum, LAP2 content diminished on diestrus and proestrus and LIP content diminished on proestrus and estrus days. In the prefrontal cortex, LIP content was higher on proestrus and estrus days. In the hippocampus, LAP isoforms presented a switch on diestrus day, since LAP1 content was the highest while that of LAP2 was the lowest. The LAP2 isoform was the most abundant one in all the three brain areas. The LAP/LIP ratio changed throughout the cycle and was tissue specific. These results suggest that C/EBPβisoforms expression changes in a tissue-specific manner in the rat brain due to the changes in sex steroid hormone levels presented during the estrous cycle.

scholarly journals In Search of Molecular Markers for Cerebellar Neurons

2021 ◽  
Vol 22 (4) ◽  
pp. 1850
Author(s):  
Wing Yip Tam ◽  
Xia Wang ◽  
Andy S. K. Cheng ◽  
Kwok-Kuen Cheung
Keyword(s):  
Cognitive Deficits ◽  
Motor Coordination ◽  
Normal Development ◽  
Genetic Manipulation ◽  
Cell Types ◽  
Functional Study ◽  
Cerebellar Neurons ◽  
The Brain ◽  
Neuronal Type

The cerebellum, the region of the brain primarily responsible for motor coordination and balance, also contributes to non-motor functions, such as cognition, speech, and language comprehension. Maldevelopment and dysfunction of the cerebellum lead to cerebellar ataxia and may even be associated with autism, depression, and cognitive deficits. Hence, normal development of the cerebellum and its neuronal circuitry is critical for the cerebellum to function properly. Although nine major types of cerebellar neurons have been identified in the cerebellar cortex to date, the exact functions of each type are not fully understood due to a lack of cell-specific markers in neurons that renders cell-specific labeling and functional study by genetic manipulation unfeasible. The availability of cell-specific markers is thus vital for understanding the role of each neuronal type in the cerebellum and for elucidating the interactions between cell types within both the developing and mature cerebellum. This review discusses various technical approaches and recent progress in the search for cell-specific markers for cerebellar neurons.

scholarly journals Tissue specific effects of ommochrome pathway mutations in Drosophila melanogaster

1991 ◽  
Vol 57 (3) ◽  
pp. 257-266 ◽  
Author(s):  
Rick Tearle
Keyword(s):  
Fat Body ◽  
Regulatory Protein ◽  
Malpighian Tubules ◽  
Normal Operation ◽  
Brown Pigment ◽  
Gene Products ◽  
Pigment Synthesis ◽  
Tissue Specific ◽  
Specific Effects

SummaryThe tissue-specific effects of 17 mutations affecting the synthesis of brown eye pigment (xanthommatin) have been investigated by combining them with chocolate and red cells, two mutations causing ectopic pigmentation of the Malpighian tubules and larval fat body (which normally only synthesize pigment precursors). The majority of mutations block the pigmentation of four organs: the normally pigmented eyes and ocelli, and ectopically pigmented tubules and fat body. They represent genes that would appear to be required for the normal operation of the pathway per se and are likely to encode structural proteins. Mutations at 5 loci affect pigmentation of a subset of organs: cd and po affect only the eyes and ocelli; kar affects the eyes, ocelli and fat body; car causes excretion of pigment from tubules; and z affects pigmentation of the eyes alone. Of these loci, only z has been shown to encode a regulatory protein and the role of the remaining four gene products is not clear. Two mutations affecting the red eye pigments (drosopterins), bw and mal, do not substantially perturb brown pigment synthesis in any of the four organs.

scholarly journals Microglial SIRPα regulates the emergence of CD11c+ microglia and demyelination damage in white matter

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Miho Sato-Hashimoto ◽  
Tomomi Nozu ◽  
Riho Toriba ◽  
Ayano Horikoshi ◽  
Miho Akaike ◽  
...  
Keyword(s):  
White Matter ◽  
Membrane Protein ◽  
Functional Role ◽  
Regulatory Protein ◽  
Genetic Ablation ◽  
Brain White Matter ◽  
Expression Of Genes ◽  
The Brain ◽  
Repair Phase

A characteristic subset of microglia expressing CD11c appears in response to brain damage. However, the functional role of CD11c+ microglia, as well as the mechanism of its induction, are poorly understood. Here we report that the genetic ablation of signal regulatory protein α (SIRPα), a membrane protein, induced the emergence of CD11c+ microglia in the brain white matter. Mice lacking CD47, a physiological ligand of SIRPα, and microglia-specific SIRPα-knockout mice exhibited the same phenotype, suggesting that an interaction between microglial SIRPα and CD47 on neighbouring cells suppressed the emergence of CD11c+ microglia. A lack of SIRPα did not cause detectable damage to the white matter, but resulted in the increased expression of genes whose expression is characteristic of the repair phase after demyelination. In addition, cuprizone-induced demyelination was alleviated by the microglia-specific ablation of SIRPα. Thus, microglial SIRPα suppresses the induction of CD11c+ microglia that have the potential to accelerate the repair of damaged white matter.

The Role of Mitochondria in the Genesis of Neuroaxonal Dystrophy in the Brains of Aging Mice

1975 ◽  
Vol 33 ◽  
pp. 372-373
Author(s):  
J.E. Johnson
Keyword(s):  
Electron Microscopy ◽  
Present Report ◽  
Light And Electron Microscopy ◽  
Dorsal Column ◽  
Neuroaxonal Dystrophy ◽  
Nucleus Gracilis ◽  
Dystrophic Axons ◽  
The Brain ◽  
Nucleus Cuneatus

Although neuroaxonal dystrophy (NAD) has been examined by light and electron microscopy for years, the nature of the components in the dystrophic axons is not well understood. The present report examines nucleus gracilis and cuneatus (the dorsal column nuclei) in the brain stem of aging mice.Mice (C57BL/6J) were sacrificed by aldehyde perfusion at ages ranging from 3 months to 23 months. Several brain areas and parts of other organs were processed for electron microscopy.At 3 months of age, very little evidence of NAD can be discerned by light microscopy. At the EM level, a few axons are found to contain dystrophic material. By 23 months of age, the entire nucleus gracilis is filled with dystrophic axons. Much less NAD is seen in nucleus cuneatus by comparison. The most recurrent pattern of NAD is an enlarged profile, in the center of which is a mass of reticulated material (reticulated portion; or RP).

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