CBLN1

Precerebellin, or CBLN1, is the precursor of a conserved brain-specific hexadecapeptide termed cerebellin. CBLN1 and other members of the precerebellin family also contain a C-terminal C1q signature domain (see 120550) that mediates trimeric assembly of atypical collagen complexes. Precerebellin is processed to give rise to several derivatives, including the hexadecapeptide, cerebellin, which is highly enriched in postsynaptic structures of Purkinje cells. However, precerebellins do not contain a collagen motif, suggesting that they are not conventional components of the extracellular matrix. Cerebellin has also been found in human and rat adrenals, where it has been shown to enhance the secretory activity of this gland.

Full Name

Cerebellin 1 precursor

Function

Required for synapse integrity and synaptic plasticity. During cerebellar synapse formation, essential for the matching and maintenance of pre- and post-synaptic elements at parallel fiber-Purkinje cell synapses, the establishment of the proper pattern of climbing fiber-Purkinje cell innervation, and induction of long-term depression at parallel fiber-Purkinje cell synapses. Plays a role as a synaptic organizer that acts bidirectionally on both pre- and post-synaptic components. On the one hand induces accumulation of synaptic vesicles in the pre-synaptic part by binding with NRXN1 and in other hand induces clustering of GRID2 and its associated proteins at the post-synaptic site through association of GRID2. NRXN1-CBLN1-GRID2 complex directly induces parallel fiber protrusions that encapsulate spines of Purkinje cells leading to accumulation of GRID2 and synaptic vesicles. Required for CBLN3 export from the endoplasmic reticulum and secretion (By similarity).
NRXN1-CBLN1-GRID2 complex mediates the D-Serine-dependent long term depression signals and AMPA receptor endocytosis (PubMed:27418511).
Essential for long-term maintenance but not establishment of excitatory synapses (By similarity).
Inhibits the formation and function of inhibitory GABAergic synapses in cerebellar Purkinje cells (By similarity).
The cerebellin peptide exerts neuromodulatory functions. Directly stimulates norepinephrine release via the adenylate cyclase/PKA-dependent signaling pathway; and indirectly enhances adrenocortical secretion in vivo, through a paracrine mechanism involving medullary catecholamine release (By similarity).

Biological Process

Cerebellar granule cell differentiation Source: BHF-UCL
Chemical synaptic transmission Source: ProtInc
Heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules Source: BHF-UCL
Maintenance of synapse structure Source: UniProtKB
Negative regulation of excitatory postsynaptic potential Source: UniProtKB
Negative regulation of inhibitory synapse assembly Source: UniProtKB
Nervous system development Source: ProtInc
Positive regulation of long-term synaptic depression Source: UniProtKB
Positive regulation of synapse assembly Source: Ensembl
Protein secretion Source: Ensembl
Regulation of postsynaptic density assembly Source: Ensembl
Regulation of presynapse assembly Source: Ensembl
Synapse organization Source: UniProtKB

Cellular Location

Secreted; Postsynaptic cell membrane

PTM

The proteolytic processing to yield cerebellin seems to occur either prior to the secretion by presynaptic neurons and subsequent oligomerization or in some other location after release of the mature protein.
Sialoglycoprotein.