scholarly journals Cell Surface Immobilization of GABAARs in Cerebellar Granule Cells Depends on the M3/M4 Cytoplasmatic Loop of the Alpha 1 Subunit

2008 ◽  
Vol 189 (6) ◽  
pp. 420-424
Author(s):  
Macarena Perán ◽  
Helen Hooper ◽  
Juan A. Marchal ◽  
Houria Boulaiz ◽  
Fernando Rodríguez-Serrano ◽  
...  
Keyword(s):  
Cell Surface ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Surface Immobilization ◽  
Cerebellar Granule

scholarly journals Heparan sulphate proteoglycans interact with neurocan and promote neurite outgrowth from cerebellar granule cells

2004 ◽  
Vol 383 (1) ◽  
pp. 129-138 ◽  
Author(s):  
Kaoru AKITA ◽  
Munetoyo TODA ◽  
Yuki HOSOKI ◽  
Mizue INOUE ◽  
Shinji FUSHIKI ◽  
...  
Keyword(s):  
Cell Surface ◽  
Neurite Outgrowth ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Heparan Sulphate ◽  
Biological Significance ◽  
Cell Surface Receptor ◽  
Adhesion Assay ◽  
Cerebellar Granule ◽  
Heparan Sulphate Proteoglycans

We found that neurocan, a major brain chondroitin sulphate proteoglycan, interacts with HSPGs (heparan sulphate proteoglycans) such as syndecan-3 and glypican-1. Binding of these HSPGs to neurocan was prevented by treatment of the HSPGs with heparitinases I and II, but not by treatment of neurocan with chondroitinase ABC. Scatchard plot analysis indicated that neurocan has two binding sites for these HSPGs with different affinities. It is known that neurocan in the rodent brain is proteolytically processed with aging into N- and C-terminal fragments. When a mixture of whole neurocan and N- and C-terminal fragments prepared from neonatal mouse brains or recombinant N- and C-terminal fragments was applied to a heparin column, the whole molecule and both the N- and C-terminal fragments bound to heparin. A centrifugation cell adhesion assay indicated that both the N- and C-terminal neurocan fragments could interact with these HSPGs expressed on the cell surface. To examine the biological significance of the HSPG–neurocan interaction, cerebellar granule cells expressing these HSPGs were cultured on the recombinant neurocan substrate. A significant increase in the rate of neurite outgrowth was observed on the wells coated with the C-terminal neurocan fragment, but not with the N-terminal one. Neurite outgrowth-promoting activity was inhibited by pretreatment of neurocan substrate with heparin or the addition of heparitinase I to culture medium. These results suggest that HSPGs such as syndecan-3 and glypican-1 serve as the cell-surface receptor of neurocan, and that the interaction of these HSPGs with neurocan through its C-terminal domain is involved in the promotion of neurite outgrowth.

scholarly journals Single-cell spatial transcriptomic analysis reveals common and divergent features of developing postnatal granule cerebellar cells and medulloblastoma

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Wenqin Luo ◽  
Guan Ning Lin ◽  
Weichen Song ◽  
Yu Zhang ◽  
Huadong Lai ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Granule Neurons ◽  
Cerebellar Granule ◽  
Granule Neuron ◽  
Proliferation And Differentiation ◽  
Single Cell Rna Sequencing ◽  
Cerebellar Cells

Abstract Background Cerebellar neurogenesis involves the generation of large numbers of cerebellar granule neurons (GNs) throughout development of the cerebellum, a process that involves tight regulation of proliferation and differentiation of granule neuron progenitors (GNPs). A number of transcriptional regulators, including Math1, and the signaling molecules Wnt and Shh have been shown to have important roles in GNP proliferation and differentiation, and deregulation of granule cell development has been reported to be associated with the pathogenesis of medulloblastoma. While the progenitor/differentiation states of cerebellar granule cells have been broadly investigated, a more detailed association between developmental differentiation programs and spatial gene expression patterns, and how these lead to differential generation of distinct types of medulloblastoma remains poorly understood. Here, we provide a comparative single-cell spatial transcriptomics analysis to better understand the similarities and differences between developing granule and medulloblastoma cells. Results To acquire an enhanced understanding of the precise cellular states of developing cerebellar granule cells, we performed single-cell RNA sequencing of 24,919 murine cerebellar cells from granule neuron-specific reporter mice (Math1-GFP; Dcx-DsRed mice). Our single-cell analysis revealed that there are four major states of developing cerebellar granule cells, including two subsets of granule progenitors and two subsets of differentiating/differentiated granule neurons. Further spatial transcriptomics technology enabled visualization of their spatial locations in cerebellum. In addition, we performed single-cell RNA sequencing of 18,372 cells from Patched+/− mutant mice and found that the transformed granule cells in medulloblastoma closely resembled developing granule neurons of varying differentiation states. However, transformed granule neuron progenitors in medulloblastoma exhibit noticeably less tendency to differentiate compared with cells in normal development. Conclusion In sum, our study revealed the cellular and spatial organization of the detailed states of cerebellar granule cells and provided direct evidence for the similarities and discrepancies between normal cerebellar development and tumorigenesis.

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