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PMID:25297099

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Citation

Jia, JM, Hu, Z, Nordman, J and Li, Z (2014) The schizophrenia susceptibility gene dysbindin regulates dendritic spine dynamics. J. Neurosci. 34:13725-36

Abstract

Dysbindin is a schizophrenia susceptibility gene required for the development of dendritic spines. The expression of dysbindin proteins is decreased in the brains of schizophrenia patients, and neurons in mice carrying a deletion in the dysbindin gene have fewer dendritic spines. Hence, dysbindin might contribute to the spine pathology of schizophrenia, which manifests as a decrease in the number of dendritic spines. The development of dendritic spines is a dynamic process involving formation, retraction, and transformation of dendritic protrusions. It has yet to be determined whether dysbindin regulates the dynamics of dendritic protrusions. Here we address this question using time-lapse imaging in hippocampal neurons. Our results show that dysbindin is required to stabilize dendritic protrusions. In dysbindin-null neurons, dendritic protrusions are hyperactive in formation, retraction, and conversion between different types of protrusions. We further show that CaMKIIα is required for the stabilization of mushroom/thin spines, and that the hyperactivity of dendritic protrusions in dysbindin-null neurons is attributed in part to decreased CaMKIIα activity resulting from increased inhibition of CaMKIIα by Abi1. These findings elucidate the function of dysbindin in the dynamic morphogenesis of dendritic protrusions, and reveal the essential roles of dysbindin and CaMKIIα in the stabilization of dendritic protrusions during neuronal development.

Links

PubMed PMC4188970 Online version:10.1523/JNEUROSCI.0184-14.2014

Keywords

Adaptor Proteins, Signal Transducing/metabolism; Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism; Calcium-Calmodulin-Dependent Protein Kinase Type 2/physiology; Cells, Cultured; Cytoskeletal Proteins/metabolism; Dendritic Spines/physiology; Dendritic Spines/ultrastructure; Dysbindin; Dystrophin-Associated Proteins/genetics; Dystrophin-Associated Proteins/physiology; Female; Male; Mice; Mice, Inbred C57BL; Protein Binding; Schizophrenia/genetics; Transfection

Significance

Annotations

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

MOUSE:KCC2A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q8CBW3

F

  • occurs_in:(CL:0002608)

Seeded From UniProt

complete

MOUSE:KCC2A

acts_upstream_of_or_within

GO:0048813: dendrite morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0002608)

Seeded From UniProt

complete

MOUSE:ABI1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P11798

F

Seeded From UniProt

complete

MOUSE:ABI1

acts_upstream_of_or_within

GO:0048813: dendrite morphogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

  • occurs_in:(CL:0002608)

Seeded From UniProt

complete

MOUSE:DTBP1

acts_upstream_of_or_within

GO:0032091: negative regulation of protein binding

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856628

P

  • occurs_in:(CL:0002608)
  • regulates_o_occurs_in:(CL:0002608)
  • regulates_o_has_input:(MGI:MGI:104913)
  • regulates_o_has_input:(MGI:MGI:88256)

Seeded From UniProt

complete

MOUSE:DTBP1

acts_upstream_of_or_within

GO:0048813: dendrite morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856628

P

  • occurs_in:(CL:0002608)

Seeded From UniProt

complete

MOUSE:DTBP1

acts_upstream_of_or_within

GO:0071901: negative regulation of protein serine/threonine kinase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856628

P

  • regulates_o_occurs_in:(CL:0002608)
  • has_input:(MGI:MGI:88256)

Seeded From UniProt

complete

MOUSE:DTBP1

acts_upstream_of_or_within

GO:0032091: negative regulation of protein binding

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856628

P

  • occurs_in:(CL:0002608)
  • regulates_o_occurs_in:(CL:0002608)
  • regulates_o_has_input:(MGI:MGI:88256)
  • regulates_o_has_input:(MGI:MGI:104913)

Seeded From UniProt

complete

MOUSE:DTBP1

acts_upstream_of_or_within

GO:0071901: negative regulation of protein serine/threonine kinase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856628

P

Seeded From UniProt

complete

MOUSE:DTBP1

acts_upstream_of_or_within

GO:0048813: dendrite morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856628

P

occurs_in:(CL:0002608)

Seeded From UniProt

complete

MOUSE:KCC2A

acts_upstream_of_or_within

GO:0048813: dendrite morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(CL:0002608)

Seeded From UniProt

complete

MOUSE:ABI1

acts_upstream_of_or_within

GO:0048813: dendrite morphogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

occurs_in:(CL:0002608)

Seeded From UniProt

complete

Notes

See also

References

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