Development of polarity in cerebellar granule neurons

Powell, Stephen Joseph; Rivas, Rodolfo J.; Rodríguez-Boulan, Enrique; Hatten, Mary E.

doi:10.1002/(sici)1097-4695(199702)32:2<223::aid-neu7>3.0.co;2-a

Cited by 103 publications

(105 citation statements)

References 52 publications

(13 reference statements)

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“…In this context, the targeted sorting mechanism in the neuron is interesting. Several studies showed the axonal sorting of some GPI-anchored proteins in cortical neurons, although dendritic sorting of some GPI-anchored proteins is reported in the granule cell of the cerebellum (61)(62)(63). According to the recent studies by Jereb and Banker (64) using viral vectors in cultured hippocampal neurons, the sorting information present in apical proteins is not sufficient to target these proteins to axons, although the dendritic sorting depends on the protein sequence.…”

Section: Discussionmentioning

confidence: 99%

Cholesterol-dependent Localization of NAP-22 on a Neuronal Membrane Microdomain (Raft)

Maékawa¹,

Sato²,

Kitajima³

et al. 1999

Journal of Biological Chemistry

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A membrane microdomain called raft has been under extensive study since the assembly of various signaltransducing molecules into this region has been envisaged. This domain is isolated as a low buoyant membrane fraction after the extraction with a nonionic detergent such as Triton X-100. The characteristic low density of this fraction is ascribed to the enrichment of several lipids including cholesterol. To clear the molecular mechanism of raft formation, several extraction methods were applied to solubilize raft components. Cholesterol extraction using methyl-␤-cyclodextrin was found to be effective to solubilize NAP-22, a neuronenriched Ca 2؉ -dependent calmodulin-binding protein as well as one of the main protein components of brain raft. Purified NAP-22 bound to the liposomes that were made from phosphatidylcholine and cholesterol. This binding was dependent on the amount of cholesterol in liposomes. Calmodulin inhibited this binding in a dosedependent manner. These results suggest that the presence of a calcium-dependent regulatory mechanism works on the assembly of raft within the neuron.

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Section: Discussionmentioning

confidence: 99%

Cholesterol-dependent Localization of NAP-22 on a Neuronal Membrane Microdomain (Raft)

Maékawa¹,

Sato²,

Kitajima³

et al. 1999

Journal of Biological Chemistry

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“…Neurite outgrowth was determined after 2 days in vitro (see below), at which time newborn rodent CGNs are primarily unipolar, with the neurite often containing a branch morphologically similar to CGN axons developing in vivo (22). Cytoskeletal-specific markers have been used to identify early extending neurites from CGNs as axons (22).…”

Section: Materials and Methods Cerebellar Granule Neurons (Cgns)mentioning

confidence: 99%

“…Cytoskeletal-specific markers have been used to identify early extending neurites from CGNs as axons (22).…”

Section: Materials and Methods Cerebellar Granule Neurons (Cgns)mentioning

confidence: 99%

Gangliosides are functional nerve cell ligands for myelin-associated glycoprotein (MAG), an inhibitor of nerve regeneration

Vyas

Patel

Fromholt

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

253

199

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Myelin-associated glycoprotein (MAG) binds to the nerve cell surface and inhibits nerve regeneration. The nerve cell surface ligand(s) for MAG are not established, although sialic acid-bearing glycans have been implicated. We identify the nerve cell surface gangliosides GD1a and GT1b as specific functional ligands for MAG-mediated inhibition of neurite outgrowth from primary rat cerebellar granule neurons. MAG-mediated neurite outgrowth inhibition is attenuated by (i) neuraminidase treatment of the neurons; (ii) blocking neuronal ganglioside biosynthesis; (iii) genetically modifying the terminal structures of nerve cell surface gangliosides; and (iv) adding highly specific IgG-class antiganglioside mAbs. Furthermore, neurite outgrowth inhibition is mimicked by highly multivalent clustering of GD1a or GT1b by using precomplexed antiganglioside Abs. These data implicate the nerve cell surface gangliosides GD1a and GT1b as functional MAG ligands and suggest that the first step in MAG inhibition is multivalent ganglioside clustering.

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“…This mouse line overexpresses ovine PrP from natural regulatory sequences under a mouse PrP 0/0 background (21). Primary culture of CGN provides a means to obtain highly enriched and homogenous populations of postmitotic neurons, which can be maintained for Ͼ1 month (26,27). Typically, cultures were mainly composed of neurons (Ͼ95%) up to 2 weeks after seeding, with 4-5% astrocytes and Ͻ1% microglial cells.…”

Section: Primary Cultures Of Mouse Cerebellar Cells Expressing Sheep mentioning

confidence: 99%

Prions can infect primary cultured neurons and astrocytes and promote neuronal cell death

Cronier

Laude

Peyrin

2004

Proc. Natl. Acad. Sci. U.S.A.

138

150

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Transmissible spongiform encephalopathies arise as a consequence of infection of the central nervous system by prions, where neurons and glial cells are regarded as primary targets. Neuronal loss and gliosis, associated with the accumulation of misfolded prion protein (PrP), are hallmarks of prion diseases; yet the mechanisms underlying such disorders remain unclear. Here we introduced a cell system based on primary cerebellar cultures established from transgenic mice expressing ovine PrP and then exposed to sheep scrapie agent. Upon exposure to low doses of infectious agent, such cultures, unlike cultures originating from PrP null mice, were found to accumulate de novo abnormal PrP and infectivity, as assessed by mouse bioassay. Importantly, using astrocyte and neuron͞astrocyte cocultures, both cell types were found capable of sustaining efficient prion propagation independently, leading to the production of proteinase K-resistant PrP of the same electrophoretic profile as in diseased brain. Moreover, contrasting with data obtained in chronically infected cell lines, late-occurring apoptosis was consistently demonstrated in the infected neuronal cultures. Our results provide evidence that primary cultured neural cells, including postmitotic neurons, are permissive to prion replication, thus establishing an approach to study the mechanisms involved in prion-triggered neurodegeneration at a cellular level.T ransmissible spongiform encephalopathies (TSE), which include Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy in cattle, and scrapie in sheep, are fatal neurodegenerative disorders caused by prions, a class of unconventional agents that targets the CNS in mammals. A hallmark of prion diseases is the accumulation of abnormal prion protein (PrP Sc ), a misfolded form of the cellular PrP (PrP c ). Transmissibility is believed to stem from the ability of the prion isoform to promote the conformational transition from PrP c to PrP Sc . Biologically distinct prion strains can propagate in a same host, presumably through the perpetuation of different specific PrP Sc conformers (1-3).Although it seems clear that neuronal dysfunction must lie at the root of the clinical disorders observed in these diseases, it is still obscure what triggers neurodegeneration and what role nonneuronal cells may play in this process. There is ample evidence to support a primary role of the neurons in prion propagation and neuropathogenesis into the CNS. Intra-or perineuronal PrP Sc deposition, spongiform vacuolation involving cell soma and processes, and neuronal loss are typical histopathological changes observed in TSE-affected brain tissues (4, 5). Transgenic mice with PrP expression specifically targeted to neurons have been obtained that turned out to be fully susceptible to prion disease (6). More recently, it was shown that an acute neuron-targeted depletion of PrP in the brain of mice with ongoing infection is able to prevent neuronal loss and progression to disease and even to reverse early spongiform chang...

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Development of polarity in cerebellar granule neurons

Cited by 103 publications

References 52 publications

Cholesterol-dependent Localization of NAP-22 on a Neuronal Membrane Microdomain (Raft)

Cholesterol-dependent Localization of NAP-22 on a Neuronal Membrane Microdomain (Raft)

Gangliosides are functional nerve cell ligands for myelin-associated glycoprotein (MAG), an inhibitor of nerve regeneration

Prions can infect primary cultured neurons and astrocytes and promote neuronal cell death

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