Cbln and C1q family proteins – New transneuronal cytokines

Yuzaki, Michisuke

doi:10.1007/s00018-008-7550-3

Cited by 70 publications

(62 citation statements)

References 44 publications

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“…Further studies are warranted to clarify the role of Cbln1 in the regulation of activity-dependent structural plasticity in adult wild-type cerebellum. Since the Cbln family (Cbln1-Cbln4) and other C1q/ TNF␣ superfamily members are expressed in various regions of the mature brain (Yuzaki, 2008), understanding the role of Cbln1 will be of great benefit for unraveling various forms of synaptic plasticity in the adult brain.…”

Section: Physiological Role Of Activity-induced Downregulation Of Cbln1mentioning

confidence: 99%

“…Cbln1 belongs to a Cbln subfamily (consisting of Cbln1-Cbln4) of the C1q/tumor necrosis factor (TNF) superfamily (Yuzaki, 2008). In the cerebellum, Cbln1 is released from granule cells and plays a crucial role in forming excitatory synapses between parallel fibers (PFs; axons of granule cells) and Purkinje cells during development; the number of PFPurkinje cell synapses decreased by 80% in mice with a disrupted cbln1 gene (cbln1 Ϫ/Ϫ ) (Hirai et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Activity-Dependent Repression of Cbln1 Expression: Mechanism for Developmental and Homeostatic Regulation of Synapses in the Cerebellum

Iijima¹,

Emi²,

Yuzaki³

2009

J. Neurosci.

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Cbln1, which belongs to the C1q/tumor necrosis factor superfamily, is released from cerebellar granule cells and plays a crucial role in forming and maintaining excitatory synapses between parallel fibers (PFs; axons of granule cells) and Purkinje cells not only during development but also in the adult cerebellum. Although neuronal activity is known to cause morphological changes at synapses, how Cbln1 signaling is affected by neuronal activity remains unclear. Here, we show that chronic stimulation of neuronal activity by elevating extracellular K ϩ levels or by adding kainate decreased the expression of cbln1 mRNA within several hours in mature granule cells in a manner dependent on L-type voltage-dependent Ca 2ϩ channels and calcineurin. Chronic activity also reduced Cbln1 protein levels within a few days, during which time the number of excitatory synapses on Purkinje cell dendrites was reduced; this activity-induced reduction of synapses was prevented by the addition of exogenous Cbln1 to the culture medium. Therefore, the activity-dependent downregulation of cbln1 may serve as a new presynaptic mechanism by which PF-Purkinje cell synapses adapt to chronically elevated activity, thereby maintaining homeostasis. In addition, the expression of cbln1 mRNA was prevented when immature granule cells were maintained in high-K ϩ medium. Since immature granule cells are chronically depolarized before migrating to the internal granule layer, this depolarization-dependent regulation of cbln1 mRNA expression may also serve as a developmental switch to facilitate PF synapse formation in mature granule cells in the internal granule layer.

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Section: Physiological Role Of Activity-induced Downregulation Of Cbln1mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Activity-Dependent Repression of Cbln1 Expression: Mechanism for Developmental and Homeostatic Regulation of Synapses in the Cerebellum

Iijima¹,

Emi²,

Yuzaki³

2009

J. Neurosci.

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“…Proteins of this superfamily, among others are involved in the classical pathway of complement activation, host defense, inflammation, apoptosis, autoimmunity, cell differentiation, organogenesis, hibernation, and insulin-resistant obesity (1). The subfamily of Cbln, on the other hand, is highly expressed in various regions of the brain and recent data suggest they belong to a new class of transneuronal regulators of synapse development and synaptic plasticity (2).…”

Section: Introductionmentioning

confidence: 99%

“…Cbln3 binds specifically to Cbln1 (6) and recently Cbln4 was identified (7) (NCBI accession number NM_175631). All members of the Cbln family form homomeric and also heteromeric complexes with each other in vitro and it was suggested that such complexes play a crucial role in normal development of the cerebellum (2,8). However, not only entire Cbln molecules are able to act as a transneuronal cytokines.…”

Section: Introductionmentioning

confidence: 99%

Cerebellin and des-cerebellin exert ACTH-like effects on corticosterone secretion and the intracellular signaling pathway gene expression in cultured rat adrenocortical cells - DNA microarray and QPCR studies

Ruciński

Ziółkowska²,

Szyszka³

et al. 2009

Int J Mol Med

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Abstract. Precerebellins (Cbln) belong to the C1q/TNF superfamily of secreted proteins which have diverse functions. They are abundantly expressed in the cerebellum, however, three of them are also expressed in the rat adrenal gland. All members of the Cbln family form homomeric and heteromeric complexes with each other in vitro and it was suggested that such complexes play a crucial role in normal development of the cerebellum. The aim of our study was to investigate whether Cbln1-derived peptides, cerebellin (CER) and des-Ser 1 -cerebellin (desCER) are involved in regulating biological functions of rat adrenocortical cells. In the primary culture of rat adrenocortical cells, 24 h exposure to CER or desCER notably stimulated corticosterone output and inhibited proliferative activity and similar effects were evoked by ACTH. To study gene transcript regulation by CER, desCER and ACTH, we applied Oligo GEArray ® DNA Microarray: Rat Signal Transduction Pathway Finder™. In relation to the control culture, 13 of the 113 transcripts present on the array were differentially expressed. These transcripts were either up-or down-regulated by ACTH and/or CER or desCER treatment. Validation of DNA Microarray data by QPCR revealed that only 5 of 13 genes studied were differentially expressed. Of those genes, Fos and Icam1 were up-regulated and Egr1 was down-regulated by ACTH, CER and desCER. The remaining two genes, Fasn (insulin signaling pathway) and Hspb1 (HSP27) (stress signaling pathway), were regulated only by CER and desCER, but not by ACTH. Thus, both CER and desCER have effects similar to and different from corticotrophin on the intracellular signaling pathway gene expression in cultured rat adrenocortical cells.

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“…Progress in molecular biology methods has allowed identification of the entire subfamily of precerebellins (Cblns), which comprises four propeptides named Cbln1-4 (2-6). Cbln-related genes are located at different chromosomes, and Cblnencoded proteins are highly conserved (4,7,8). All of them are highly expressed in the central nervous system, particularly in the cerebellum.…”

Section: Introductionmentioning

confidence: 99%

Precerebellin-related genes and precerebellin 1 peptide in the adrenal gland of the rat: Expression pattern, localization, developmental regulation and effects on corticosteroidogenesis

Ruciński

Ziółkowska²,

Szyszka³

et al. 2009

Int J Mol Med

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Abstract. Precerebellin (Cbln)-related peptides are known to modulate the secretory activity and growth of the adrenal gland. However, precise expression of the Cbln-related genes and Cbln1 peptide in the adrenal remains unclear. Therefore, we investigated, using RT-PCR, QPCR, Western blotting, immunohistochemistry and hormonal assays, their expression in the adrenals of adult rats and in the course of postnatal ontogenesis. Of the 4 known Cblns, Cbln(1-3) mRNAs were found in the adrenal gland of the adult male rats. Expression patterns of Cbln1 and 3 were similar to each other and different from that of Cbln2. Highest expression of the Cbln1 and 3 genes was observed in the zona glomerulosa (ZG), lower expression was noted in the fasciculata/reticularis and lowest expression was observed in the adrenal medulla. Expression of these genes was also present in freshly isolated rat adrenocortical cells. On the contrary, by means of classic RT-PCR, we demonstrated the presence of mRNAs of CBLN(1-4) in the human adrenal gland. In the rat, highest expression of the Cbln1 and 3 genes was found at postnatal day 2 and was somewhat lower at day 90. On the contrary, expression of the Cbln2 gene was low in adrenals of 2-day-old rats and notably higher at the remaining time points studied (up to day 360). Cerebellin (CER)-like immunoreactivity was observed in the membranes of the adrenal ZG cells, while in the medulla, immunoreactive substances were localized primarily in the cytoplasm of chromaffin cells. Cbln1-like immunoreactivity was present mainly in the cortex of the gland, and reaction products were noted both in the membranes and cytoplasm of adrenocortical cells. Semiquantitative evaluation of Cbln1 protein expression in compartments of the adrenal gland of the adult rat revealed a higher concentration of Cbln1 protein in the cortex than in the medulla of studied rats. We also found that both CER and desCER stimulated basal aldosterone secretion by freshly isolated ZG cells. Thus, the present study provided precise data on expression of the Cbln-related genes and Cbln1 peptide in the adrenal gland of the rat and on their developmental regulation. We also found that, contrary to the human adrenal, in the rat adrenal gland, the Cbln4 gene was not expressed at the mRNA level.

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Cbln and C1q family proteins – New transneuronal cytokines

Cited by 70 publications

References 44 publications

Activity-Dependent Repression of Cbln1 Expression: Mechanism for Developmental and Homeostatic Regulation of Synapses in the Cerebellum

Activity-Dependent Repression of Cbln1 Expression: Mechanism for Developmental and Homeostatic Regulation of Synapses in the Cerebellum

Cerebellin and des-cerebellin exert ACTH-like effects on corticosterone secretion and the intracellular signaling pathway gene expression in cultured rat adrenocortical cells - DNA microarray and QPCR studies

Precerebellin-related genes and precerebellin 1 peptide in the adrenal gland of the rat: Expression pattern, localization, developmental regulation and effects on corticosteroidogenesis

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