Precerebellin is a cerebellum-specific protein with similarity to the globular domain of complement C1q B chain.

Abstract

The cerebellum contains a hexadecapeptide, termed cerebellin, that is conserved in sequence from human to chicken. Three independent, overlapping cDNA clones have been isolated from a human cerebellum cDNA library that encode the cerebellin sequence. The longest clone codes for a protein of 193 amino acids that we term precerebellin. This protein has a significant similarity (31.3% identity, 52.2% similarity) to the globular (non-collagen-like) region of the B chain of human complement component Clq. The region of relatedness extends over =145 amino acids located in the carboxyl terminus of both proteins. Unlike Clq B chain, no collagen-like motifs are present in the amino-terminal regions of precerebellin. The amino terminus of precerebellin contains three possible N-linked glycosylation sites. Although hydrophobic amino acids are clustered at the amino terminus, they do not conform to the classical signal-peptide motif, and no other obvious membrane-spanning domains are predicted from the cDNA sequence. The cDNA predicts that the cerebellin peptide is flanked by Val-Arg and Glu-Pro residues. Therefore, cerebellin is not liberated from precerebellin by the classical dibasic amino acid proteolytic-cleavage mechanism seen in many neuropeptide precursors. In Northern (RNA) blots, precerebellin transcripts, with four distinct sizes (1.8, 2.3, 2.7, and 3.0 kilobases), are abundant in cerebellum. These transcripts are present at either very low or undetectable levels in other brain areas and extraneural structures. A similar pattern of cerebellin precursor transcripts are seen in rat, mouse, and human cerebellum. Furthermore, a partial genomic fragment from mouse shows the same bands in Northern blots as the human cDNA clone. During rat development, precerebellin transcripts mirror the level of cerebellin peptide. Low levels of precerebellin mRNA are seen at birth. Levels increase modestly from postpartum day 1 to 8, then increase more dramatically between day 5 and 15, and eventually reach peak values between day 21 and 56. Because cerebellin-like immunoreactivity is associated with Purki'ije cell postsynaptic structures, these data raise interesting possibilities concerning the function of the cerebellin precursor in synaptic physiology.

Chronic Nicotine Treatment Impacts the Regulation of Opioid and Non-opioid Peptides in the Rat Dorsal Striatum

“…Similarly, we also found a significant increase of cerebellin (36%, p ϭ 0.016). Cerebellin is a peptide derived from its precursor, which is required for synapse integrity and synaptic plasticity (38,39). DISCUSSION Our present peptidome study explored the effects of chronic nicotine on neuropeptides levels in the DS.…”

EMILIN, a Component of the Elastic Fiber and a New Member of the C1q/Tumor Necrosis Factor Superfamily of Proteins

“…Alignment of Sequences at the C-terminal Domain-The C terminus of EMILIN exhibits a striking homology to a gC1q-like domain of a number of proteins including the A, B, and C chains of human and mouse complement C1q protein (39,40), the ␣1 and ␣2 chains of type VIII (41,42), and the ␣1 chain of type X (43) collagens, precerebellin (44), multimerin (24), ACRP-30/AdipoQ (45,46), the HP-27 protein from Siberian chipmunks (47), and a sunfish saccular collagen (48). The length of this domain is included between 131 (gC1q-C) and 151 (EMILIN) residues, and the protein sequence comparison of the C1q-like domain of EMILIN with the known similar domains indicates a high level of conservation of several hydrophobic and uncharged residues (Fig.…”

The cell-adhesion G protein-coupled receptor BAI3 is a high-affinity receptor for C1q-like proteins

“…C1ql proteins are composed of an N-terminal signal peptide followed by a short conserved sequence (∼15 residues) with two closely spaced cysteine residues, a spacer (15-35 residues), a collagen-like sequence (∼50 residues), and a C-terminal gC1q domain (∼140 residues) that accounts for approximately half of the total C1ql sequence (238-287 residues). Structurally, C1ql proteins resemble a combination of cerebellins and adiponectin, both of which contain C-terminal gC1q domains, but with either a short conserved N-terminal cysteine-rich sequence (cerebellin) or an N-terminal collagen-like sequence (adiponectin) (35,36). Notably, in cerebellins, the N-terminal sequence multimerizes the C-terminal trimeric gC1q domains (37); this sequence likely does the same in C1ql proteins (31).…”