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PMID:17030622

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Citation

Bao, D, Pang, Z, Morgan, MA, Parris, J, Rong, Y, Li, L and Morgan, JI (2006) Cbln1 is essential for interaction-dependent secretion of Cbln3. Mol. Cell. Biol. 26:9327-37

Abstract

Cbln1 and the orphan glutamate receptor GluRdelta2 are pre- and postsynaptic components, respectively, of a novel transneuronal signaling pathway regulating synapse structure and function. We show here that Cbln1 is secreted from cerebellar granule cells in complex with a related protein, Cbln3. However, cbln1- and cbln3-null mice have different phenotypes and cbln1 cbln3 double-null mice have deficits identical to those of cbln1 knockout mice. The basis for these discordant phenotypes is that Cbln1 and Cbln3 reciprocally regulate each other's degradation and secretion such that cbln1-null mice lack both Cbln1 and Cbln3, whereas cbln3-null mice lack Cbln3 but have an approximately sixfold increase in Cbln1. Unlike Cbln1, Cbln3 cannot form homomeric complexes and is secreted only when bound to Cbln1. Structural modeling and mutation analysis reveal that, by constituting a steric clash that is masked upon binding Cbln1 in a "hide-and-run" mechanism of endoplasmic reticulum retention, a single arginine confers the unique properties of Cbln3.

Links

PubMed PMC1698530 Online version:10.1128/MCB.01161-06

Keywords

Amino Acid Sequence; Animals; Cells, Cultured; Endoplasmic Reticulum/metabolism; Mice; Mice, Knockout; Molecular Sequence Data; Nerve Tissue Proteins/deficiency; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Nerve Tissue Proteins/physiology; Nerve Tissue Proteins/secretion; Phenotype; Protein Binding; Protein Precursors/deficiency; Protein Precursors/genetics; Protein Precursors/metabolism; Protein Precursors/physiology; Protein Precursors/secretion

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:CBLN4

acts_upstream_of_or_within

GO:0009306: protein secretion

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CBLN3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q9R171

F

Seeded From UniProt

complete

MOUSE:CBLN3

located_in

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:17787)
  • adjacent_to:(CL:0001031)

Seeded From UniProt

complete

MOUSE:CBLN1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q9JHG0

F

Seeded From UniProt

complete

MOUSE:CBLN1

acts_upstream_of_or_within

GO:0009306: protein secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0001031)

Seeded From UniProt

complete


See also

References

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