Disease relevance of CBLN3

• Cerebellin mRNA was also expressed in other regions of the brain and the tumour tissues of phaeochromocytoma, cortisol-producing adrenocortical adenoma, ganglioneuroblastoma and neuroblastoma [1].
• These findings suggest important pathophysiological roles of cerebellin and CRH in these cerebellar diseases [2].
• Decrease in cerebellin and corticotropin-releasing hormone in the cerebellum of olivopontocerebellar atrophy and Shy-Drager syndrome [2].

High impact information on CBLN3

• Therefore, cerebellin is not liberated from precerebellin by the classical dibasic amino acid proteolytic-cleavage mechanism seen in many neuropeptide precursors [3].
• Three independent, overlapping cDNA clones have been isolated from a human cerebellum cDNA library that encode the cerebellin sequence [3].
• Cerebellin enhances in vitro secretory activity of human adrenal gland [4].
• Cerebellin concentration dependently increased basal catecholamine (norepinephrine and epinephrine) release by human adrenal slices, containing medullary chromaffin tissue, minimal and maximal effective concentrations being 10(-9) and 10(-7) mol/L [4].
• Cerebellin did not affect basal steroid secretion of dispersed human adrenocortical cells, but it concentration dependently increased aldosterone and cortisol production by adrenal slices [4].

Biological context of CBLN3

• The cerebellum-specific hexadecapeptide, cerebellin, is derived from a larger precursor, precerebellin, that has sequence homology to the complement component C1qB [5].
• Cerebellin in the rat adrenal gland: gene expression and effects of CER and [des-Ser1]CER on the secretion and growth of cultured adrenocortical cells [6].

Anatomical context of CBLN3

• Cerebellin immunoreactivity is localized to Purkinje cells in the rat, mouse, and chicken [7].
• Immunocytochemistry of the normal adrenal gland showed that immunoreactive cerebellin was localized in the adrenal medulla [1].
• Since the cerebellins are localized in Purkinje cells and enriched in synaptosomes, this might indicate that cerebellin is a specific proteolytic cleavage fragment of a synaptic protein involved in the transcytosis of an unknown ligand [7].
• Cerebellin is a 16-aminoacid peptide widely distributed in the central nervous system, where it exerts neuromodulatory functions [8].
• Cerebellin did not affect aldosterone and corticosterone secretion of dispersed zona glomerulosa and zona fasciculata-reticularis adrenocortical cells [8].

Associations of CBLN3 with chemical compounds

• Cleavage at the N-terminus of the cerebellin sequence in Cbln1 yields trimeric complexes by separating the trimer-mediating C-terminal C1q domain from conserved N-terminal cysteine residues that mediate higher order oligomerization [9].
• Cerebellin concentration-dependently (from 10(-9)to 10(-7)M) increased norepinephrine (but not epinephrine) and cyclic-AMP production by adrenomedullary tissue in vitro [8].
• Cerebellin (10(-7)M) also elicited a significant rise in aldosterone and corticosterone output, and this effect was annulled by either the beta1-adrenoceptor antagonist l -alprenolol or H-89 [8].
• Collectively, the present findings allow us to conclude that cerebellin 1) directly stimulates norepinephrine release via the adenylate cyclase/PKA-dependent signaling pathway; and 2) indirectly enhances adrenocortical secretion in vivo, through a paracrine mechanism involving medullary catecholamine release [8].
• The norepinephrine response to 10(-7)M cerebellin was blocked by the protein kinase (PK) A inhibitor H-89, but not by the phospholipase C inhibitor U-73122 or the PKC inhibitor calphostin-C [8].

Other interactions of CBLN3

• Significant decreases in cerebellin and CRH concentrations were found in the cerebellar hemisphere of these diseases compared with controls [2].

Analytical, diagnostic and therapeutic context of CBLN3

• These peptides were, therefore, isolated by a combination of ion-exchange and reverse-phase chromatography using a specific radioimmunoassay against rat cerebellin [10].
• Northern blot analysis showed that cerebellin mRNA was highly expressed in the hemisphere and vermis of the cerebellum [1].
• Using a specific cerebellin radioimmunoassay described here combined with high-performance liquid chromatography, cerebellin immunoreactivity could be demonstrated in the cerebella of all vertebrates examined from man to chicken [7].

References