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1.
Neuron ; 99(2): 329-344.e7, 2018 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-29983322

RESUMO

Pyramidal neurons express rich repertoires of leucine-rich repeat (LRR)-containing adhesion molecules with similar synaptogenic activity in culture. The in vivo relevance of this molecular diversity is unclear. We show that hippocampal CA1 pyramidal neurons express multiple synaptogenic LRR proteins that differentially distribute to the major excitatory inputs on their apical dendrites. At Schaffer collateral (SC) inputs, FLRT2, LRRTM1, and Slitrk1 are postsynaptically localized and differentially regulate synaptic structure and function. FLRT2 controls spine density, whereas LRRTM1 and Slitrk1 exert opposing effects on synaptic vesicle distribution at the active zone. All LRR proteins differentially affect synaptic transmission, and their combinatorial loss results in a cumulative phenotype. At temporoammonic (TA) inputs, LRRTM1 is absent; FLRT2 similarly controls functional synapse number, whereas Slitrk1 function diverges to regulate postsynaptic AMPA receptor density. Thus, LRR proteins differentially control synaptic architecture and function and act in input-specific combinations and a context-dependent manner to specify synaptic properties.


Assuntos
Glicoproteínas de Membrana/fisiologia , Proteínas de Membrana/fisiologia , Moléculas de Adesão de Célula Nervosa/fisiologia , Sinapses/fisiologia , Animais , Células Cultivadas , Técnicas de Cocultura , Potenciais Pós-Sinápticos Excitadores/fisiologia , Feminino , Células HEK293 , Humanos , Masculino , Glicoproteínas de Membrana/análise , Glicoproteínas de Membrana/ultraestrutura , Proteínas de Membrana/análise , Proteínas de Membrana/ultraestrutura , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Moléculas de Adesão de Célula Nervosa/análise , Moléculas de Adesão de Célula Nervosa/ultraestrutura , Ratos , Ratos Wistar , Sinapses/química , Sinapses/ultraestrutura , Transmissão Sináptica/fisiologia
2.
Mol Cell Neurosci ; 24(4): 939-50, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14697660

RESUMO

Activity-dependent changes in expression and localization of the largest major isoform of the neural cell adhesion molecule NCAM180 and three subtypes of glutamate receptors predominantly expressed in the outer part of the molecular layer of the dentate gyrus of adult rats-the NMDA receptor NR2A, the AMPA receptor GluR2/3, and the metabotropic glutamate receptor mGluR1 - were investigated using postembedding immunogold labeling, and electron microscopy. In synaptic membranes of nonstimulated spine synapses, NCAM180 and NR2A accumulated in the center of the postsynaptic density, whereas GluR2/3 and mGluR1 were distributed evenly. Twenty-four hours following induction of long-term potentiation in vivo, NCAM180 and NR2A accumulated at the edges of postsynaptic densities, whereas GluR2/3 was localized more centrally. Also, the distribution of gold particles per synapse significantly changed for NCAM180, NR2A, and mGluR1. Thus, changes in synaptic strength are associated with concomitant changes in the expression and distribution of NCAM180 and glutamate receptors, particularly of the NR2A subtype.


Assuntos
Potenciação de Longa Duração/fisiologia , Microscopia Imunoeletrônica/métodos , Moléculas de Adesão de Célula Nervosa/análise , Receptores de Glutamato/análise , Sinapses/química , Animais , Giro Denteado/química , Giro Denteado/fisiologia , Giro Denteado/ultraestrutura , Imuno-Histoquímica , Masculino , Moléculas de Adesão de Célula Nervosa/fisiologia , Moléculas de Adesão de Célula Nervosa/ultraestrutura , Isoformas de Proteínas/análise , Isoformas de Proteínas/fisiologia , Isoformas de Proteínas/ultraestrutura , Ratos , Ratos Wistar , Receptores de AMPA/análise , Receptores de AMPA/fisiologia , Receptores de AMPA/ultraestrutura , Receptores de Glutamato/fisiologia , Receptores de Glutamato/ultraestrutura , Receptores de Glutamato Metabotrópico/análise , Receptores de Glutamato Metabotrópico/fisiologia , Receptores de Glutamato Metabotrópico/ultraestrutura , Receptores de N-Metil-D-Aspartato , Sinapses/fisiologia , Sinapses/ultraestrutura
3.
J Neurosci Res ; 66(3): 347-55, 2001 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-11746352

RESUMO

The neural cell adhesion molecule L1 contains immunoglobulin-like (Ig) domains in its extracellular region that mediate homophilic binding, neurite outgrowth and other activities relevant to CNS development. To correlate conformations of these domains to biological function, several L1-Fc fusion proteins whose bioactivities were previously characterized were analyzed by rotary shadowing electron microscopy. We found that bioactive L1-Fcs containing Ig domains 1-4 or 1-6 exhibited extended, branched structures. In contrast, inactive L1-Fcs containing only the first two or three Ig domains assumed compact shapes that suggested interactions between the L1 arms of these proteins. Analysis of an untagged L1 fragment composed of Ig domains 1-3 demonstrated a mixture of monomeric and dimeric forms. Surprisingly, these dimers were stabilized by intermolecular disulfide bonds. Finally, cell surface L1-GFP fusion proteins containing only the first two or three Ig domains in the extracellular region also engaged in disulfide-mediated dimerization. These results suggest a novel mechanism by which mutations in L1 could interfere with its biological functioning.


Assuntos
Sistema Nervoso Central/metabolismo , Dissulfetos/metabolismo , Imunoglobulinas/metabolismo , Imunoglobulinas/ultraestrutura , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/ultraestrutura , Moléculas de Adesão de Célula Nervosa/metabolismo , Moléculas de Adesão de Célula Nervosa/ultraestrutura , Dobramento de Proteína , Sítios de Ligação/fisiologia , Sistema Nervoso Central/embriologia , Sistema Nervoso Central/crescimento & desenvolvimento , Dimerização , Proteínas de Fluorescência Verde , Indicadores e Reagentes/metabolismo , Complexo Antígeno L1 Leucocitário , Proteínas Luminescentes/genética , Microscopia Eletrônica , Mutação/fisiologia , Malformações do Sistema Nervoso/etiologia , Malformações do Sistema Nervoso/metabolismo , Malformações do Sistema Nervoso/fisiopatologia , Estrutura Terciária de Proteína/fisiologia , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes de Fusão/ultraestrutura
4.
Braz. j. med. biol. res ; 34(5): 669-673, May 2001. ilus
Artigo em Inglês | LILACS | ID: lil-285876

RESUMO

Neurons from the anterior subventricular zone (SVZ) of the cerebral cortex migrate tangentially to become interneurons in the olfactory bulb during development and in adult rodents. This migration was defined as neuronophilic, independent of a radial glial substrate. The cortical SVZ and the rostral migratory stream to the olfactory bulb were shown to be rich in 9-O-acetyl GD3 gangliosides (9-O-acGD3), which have been previously shown to be implicated in gliophilic migration in the rodent cerebral cortex and cerebellum. In the present study, we performed SVZ explant cultures using rats during their first postnatal week to analyze the expression of these gangliosides in chain migration of neuronal precursors. We characterized migrating chains of these neuroblasts through morphological analysis and immunocytochemistry for the neural cell adhesion molecule. By using the Jones monoclonal antibody which binds specifically to 9-O-acGD3 we showed that migrating chains from the SVZ explants express 9-O-acGD3 which is distributed in a punctate manner in individual cells. 9-O-acGD3 is also present in migrating chains that form in the absence of radial glia, typical of the neuronophilic chain migration of the SVZ. Our data indicate that 9-O-acetylated gangliosides may participate in neuronophilic as well as gliophilic migration


Assuntos
Animais , Ratos , Movimento Celular/fisiologia , Córtex Cerebral/metabolismo , Gangliosídeos/metabolismo , Técnicas In Vitro , Moléculas de Adesão de Célula Nervosa/análise , Neurônios/metabolismo , Córtex Cerebral/citologia , Ventrículos Cerebrais/citologia , Moléculas de Adesão de Célula Nervosa/ultraestrutura , Neuroglia/citologia , Neurônios/ultraestrutura
5.
J Biol Chem ; 275(48): 37984-92, 2000 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-10964914

RESUMO

The macrophage fusion receptor (MFR), also called P84/BIT/SIRPalpha/SHPS-1, is a transmembrane glycoprotein that belongs to the superfamily of immunoglobulins. Previously, we showed that MFR expression is highly induced at the onset of fusion in macrophages, and that MFR appears to play a role in macrophage-macrophage adhesion/fusion leading to multinucleation. The recent finding that IAP/CD47 acts as a ligand for MFR led us to hypothesize that it interacts with CD47 at the onset of cell-cell fusion. CD47 is a transmembrane glycoprotein, which, like MFR, belongs to the superfamily of immunoglobulins. We show that macrophages express the hemopoietic form of CD47, the expression of which is induced at the onset of fusion, but to a lower level than MFR. A glutathione S-transferase CD47 fusion protein engineered to contain the extracellular domain of CD47, binds macrophages, associates with MFR, and prevents multinucleation. CD47 and MFR associate via their amino-terminal immunoglobulin variable domain. Of the nine monoclonal antibodies raised against the extracellular domain of CD47, three block fusion, as well as MFR-CD47 interaction, whereas the others have no effect. Together, these data suggest that CD47 is involved in macrophage multinucleation by virtue of interacting with MFR during adhesion/fusion.


Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação , Proteínas de Transporte/metabolismo , Núcleo Celular/ultraestrutura , Macrófagos/metabolismo , Glicoproteínas de Membrana/metabolismo , Molécula L1 de Adesão de Célula Nervosa , Moléculas de Adesão de Célula Nervosa/metabolismo , Receptores Imunológicos , Animais , Anticorpos Monoclonais/imunologia , Antígenos CD/imunologia , Sequência de Bases , Antígeno CD47 , Proteínas de Transporte/imunologia , Fusão Celular , Primers do DNA , Ligantes , Macrófagos/ultraestrutura , Glicoproteínas de Membrana/ultraestrutura , Moléculas de Adesão de Célula Nervosa/ultraestrutura , Ratos
6.
Anat Rec ; 256(4): 448-57, 1999 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-10589030

RESUMO

The suprachiasmatic nuclei (SCN) of the anterior hypothalamus are recognized as the principal circadian clock in mammals. The adult SCN express a high level of polysialylated neural cell adhesion molecule (PSA-NCAM), a cell surface sialoglycoprotein capable of modulating cell-cell interactions. In the present study, the expression of PSA-NCAM in the mouse SCN was studied at the ultrastructural level by immunolabeling using monoclonal antibodies against the polysialic acid (PSA) moiety of PSA-NCAM. We showed that neuronal somal expression of PSA-NCAM was distributed heterogeneously in the SCN, with extensive staining of somas in the central region of the SCN, and minimal somal staining in the ventral portion of the nuclei. In contrast, immunoreactive neuropil, including unmyelinated fine axon fascicles was distributed throughout the SCN. The PSA-NCAM was also detected adjacent to synaptic junctions by both immunoperoxidase and immunogold techniques. For astrocytes, immunostaining of somas and larger processes was sparse, but staining was profuse along fine processes. Immunostained fine astrocytic processes were frequently observed between apposing neuronal somas, and in close association with synaptic junctions and small blood vessels. These findings, together with the demonstrated role of PSA-NCAM in modulating cell-cell interactions in other brain regions support a role for PSA-NCAM in regulating cell-cell interactions in the SCN.


Assuntos
Moléculas de Adesão de Célula Nervosa/ultraestrutura , Polissacarídeos/metabolismo , Ácidos Siálicos/metabolismo , Núcleo Supraquiasmático/ultraestrutura , Animais , Anticorpos Monoclonais , Astrócitos/metabolismo , Astrócitos/ultraestrutura , Ritmo Circadiano , Técnica Indireta de Fluorescência para Anticorpo , Técnicas Imunoenzimáticas , Masculino , Camundongos , Microscopia de Fluorescência , Moléculas de Adesão de Célula Nervosa/metabolismo , Neurônios/metabolismo , Neurônios/ultraestrutura , Núcleo Supraquiasmático/metabolismo
7.
J Neurobiol ; 32(7): 643-58, 1997 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-9183743

RESUMO

Although N-CAM has previously been implicated in the growth and fasciculation of axons, the development of axon tracts in transgenic mice with a targeted deletion of the 180-kD isoform of the neural cell adhesion molecule (N-CAM-180) appears grossly normal in comparison to wild-type mice. We examined the organization of the olfactory nerve projection from the olfactory neuroepithelium to glomeruli in the olfactory bulb of postnatal N-CAM-180 null mutant mice. Immunostaining for olfactory marker protein revealed the normal presence of fully mature primary olfactory neurons within the olfactory neuroepithelium of mutant mice. The axons of these neurons form an olfactory nerve, enter the nerve fiber layer of the olfactory bulb, and terminate in olfactory glomeruli as in wild-type control animals. The olfactory bulb is smaller and the nerve fiber layer is relatively thicker in mutants than in wild-type mice. Previous studies have revealed that the plant lectin Dolichos biflorus agglutinin (DBA) clearly stains the perikarya and axons of a subpopulation of primary olfactory neurons. Thus, DBA staining enabled the morphology of the olfactory nerve pathway to be examined at higher resolution in both control and mutant animals. Despite a normal spatial pattern of DBA-stained neurons within the nasal cavity, there was a distorted axonal projection of these neurons onto the surface of the olfactory bulb in N-CAM-180 null mutants. In particular, DBA-stained axons formed fewer and smaller glomeruli in the olfactory bulbs of mutants in comparison to wild-type mice. Many primary olfactory axons failed to exit the nerve fiber layer and contribute to glomerular formation. These results indicate that N-CAM-180 plays an important role in the growth and fasciculation of primary olfactory axons and is essential for normal development of olfactory glomeruli.


Assuntos
Axônios/ultraestrutura , Moléculas de Adesão de Célula Nervosa/ultraestrutura , Bulbo Olfatório/ultraestrutura , Condutos Olfatórios/ultraestrutura , Animais , Imuno-Histoquímica , Camundongos , Camundongos Mutantes , Camundongos Transgênicos , Microscopia Eletrônica
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