| 2000 |
CBLN3 was identified as a novel binding partner of CBLN1 via yeast two-hybrid screen. CBLN1 binds avidly to CBLN3 and also forms homomeric complexes, whereas CBLN3 homomeric association is weak. This interaction is specific, as C1qB bound neither CBLN1 nor CBLN3. |
Yeast two-hybrid screen, protein interaction assays |
The Journal of neuroscience |
Medium |
10964938
|
| 2006 |
CBLN3 is secreted from cerebellar granule cells only when bound to CBLN1 (interaction-dependent secretion). In cbln1-null mice, Cbln3 is completely absent (degraded), whereas in cbln3-null mice, Cbln1 levels increase approximately sixfold. CBLN3 cannot form homomeric complexes and is retained in the endoplasmic reticulum when expressed alone. A single arginine residue in CBLN3 creates a steric clash that is masked upon Cbln1 binding ('hide-and-run' ER retention mechanism), conferring its unique secretion dependency. |
Knockout mouse analysis (cbln1-null, cbln3-null, double-null), structural modeling, site-directed mutagenesis, cell secretion assays |
Molecular and cellular biology |
High |
17030622
|
| 2007 |
When expressed alone in mammalian heterologous cells, CBLN3 is not secreted but is retained in the endoplasmic reticulum or cis-Golgi due to its N-terminal domain. Co-expression of CBLN1 and CBLN3 results in partial secretion of CBLN3 together with CBLN1. In wild-type granule cells (which co-express CBLN1 and CBLN3), CBLN3 is partially secreted and reaches postsynaptic sites on Purkinje cell dendrites; in cbln1-null granule cells, CBLN3 is almost completely degraded. |
Heterologous cell expression, co-expression assays, immunohistochemistry in wild-type and cbln1-null granule cells |
The European journal of neuroscience |
High |
17331201
|
| 2006 |
CBLN3 mRNA expression in the brain is selective to cerebellar granule cells throughout development, with onset as late as postnatal day 7-10, distinguishing it from other Cbln family members which appear earlier in development. |
RT-PCR, Northern blot, high-resolution in situ hybridization |
The European journal of neuroscience |
Medium |
16930405
|
| 2009 |
CBLN1 and CBLN3 co-localize with GluRdelta2 at parallel fiber-Purkinje cell synaptic clefts, as revealed by antigen-exposing immunohistochemical methods. CBLN1 accumulates in the synaptic cleft specifically at PF-PC synapses (not at other PC synapses), and co-localizes almost completely with CBLN3 and GluRdelta2 at these sites. |
Light and electron microscopic immunohistochemistry with pepsin pretreatment and postembedding immunogold |
The European journal of neuroscience |
Medium |
19250438
|
| 2007 |
In cbln3-null mice, CBLN1-like immunoreactivity in the cerebellum is dramatically increased (consistent with CBLN1 upregulation when not complexed with CBLN3), but CLI is unchanged in extracerebellar neurons. CBLN1 localizes to the endolysosomal compartment (co-localizing with cathepsin D) in neurons, suggesting that regulated degradation of Cbln proteins occurs through endosome/lysosome processing. |
Immunohistochemistry, cbln1-lacZ transgenic mice, cbln3-null mice, co-localization with lysosomal marker cathepsin D |
The European journal of neuroscience |
Medium |
18001291
|
| 2017 |
CBLN3 requires CBLN1 for assembly and secretion, unlike CBLN1, CBLN2, and CBLN4 which autonomously assemble into homohexamers. This property distinguishes CBLN3 functionally from other cerebellin family members. |
Biochemical assembly and secretion assays in heterologous expression systems, knockin reporter mice |
The Journal of comparative neurology |
Medium |
28714144
|