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PMID:18054859

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Citation

Samuels, BA, Hsueh, YP, Shu, T, Liang, H, Tseng, HC, Hong, CJ, Su, SC, Volker, J, Neve, RL, Yue, DT and Tsai, LH (2007) Cdk5 promotes synaptogenesis by regulating the subcellular distribution of the MAGUK family member CASK. Neuron 56:823-37

Abstract

Synaptogenesis is a highly regulated process that underlies formation of neural circuitry. Considerable work has demonstrated the capability of some adhesion molecules, such as SynCAM and Neurexins/Neuroligins, to induce synapse formation in vitro. Furthermore, Cdk5 gain of function results in an increased number of synapses in vivo. To gain a better understanding of how Cdk5 might promote synaptogenesis, we investigated potential crosstalk between Cdk5 and the cascade of events mediated by synapse-inducing proteins. One protein recruited to developing terminals by SynCAM and Neurexins/Neuroligins is the MAGUK family member CASK. We found that Cdk5 phosphorylates and regulates CASK distribution to membranes. In the absence of Cdk5-dependent phosphorylation, CASK is not recruited to developing synapses and thus fails to interact with essential presynaptic components. Functional consequences include alterations in calcium influx. Mechanistically, Cdk5 regulates the interaction between CASK and liprin-alpha. These results provide a molecular explanation of how Cdk5 can promote synaptogenesis.

Links

PubMed PMC2151975 Online version:10.1016/j.neuron.2007.09.035

Keywords

Animals; Autistic Disorder/genetics; Calcium Channels/physiology; Cell Adhesion Molecules; Cyclin-Dependent Kinase 5/physiology; Guanylate Kinase/metabolism; Immunoglobulins/biosynthesis; Immunoglobulins/genetics; Ion Channel Gating/physiology; Membrane Proteins/biosynthesis; Membrane Proteins/genetics; Mice; Phosphorylation; Presynaptic Terminals/physiology; Proteins/genetics; Receptor Cross-Talk/physiology; Subcellular Fractions/metabolism; Synapses/physiology

Significance

Annotations

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

MOUSE:APBA1

part_of

GO:0016020: membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:APBA1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:O70589

F

Seeded From UniProt

complete

MOUSE:CAC1B

part_of

GO:0016020: membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CAC1B

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:O70589

F

Seeded From UniProt

complete

MOUSE:CSKP

acts_upstream_of_or_within

GO:0070509: calcium ion import

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000540)

Seeded From UniProt

complete

MOUSE:CSKP

enables

GO:0042043: neurexin family protein binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_in:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:CSKP

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q8JZS0

F

Seeded From UniProt

complete

MOUSE:CSKP

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q8BSS9

F

Seeded From UniProt

complete

MOUSE:CSKP

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P61809

F

Seeded From UniProt

complete

MOUSE:CSKP

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P49615

F

Seeded From UniProt

complete

MOUSE:CSKP

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:O55017

F

Seeded From UniProt

complete

MOUSE:CSKP

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:B2RUJ5

F

Seeded From UniProt

complete

MOUSE:CDK5

acts_upstream_of_or_within

GO:0070509: calcium ion import

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000540)

Seeded From UniProt

complete

MOUSE:CDK5

enables

GO:0004674: protein serine/threonine kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(MGI:MGI:1309489)|has_input:(MGI:MGI:1932915)

Seeded From UniProt

complete

MOUSE:CDK5

acts_upstream_of_or_within

GO:0035418: protein localization to synapse

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:CDK5

acts_upstream_of_or_within

GO:0007416: synapse assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:CDK5

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:O70589

F

Seeded From UniProt

complete

MOUSE:CD5R1

acts_upstream_of_or_within

GO:0090314: positive regulation of protein targeting to membrane

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CD5R1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:O70589

F

Seeded From UniProt

complete

MOUSE:LIPA2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:O70589

F

Seeded From UniProt

complete

MOUSE:LIN7A

part_of

GO:0016020: membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:LIN7A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:O70589

F

Seeded From UniProt

complete

MOUSE:NMDE1

part_of

GO:0016020: membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CSKP

acts_upstream_of_or_within

GO:0090280: positive regulation of calcium ion import

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CSKP

part_of

GO:0045202: synapse

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CSKP

part_of

GO:0016020: membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CSKP

acts_upstream_of_or_within

GO:0070509: calcium ion import

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(CL:0000540)

Seeded From UniProt

complete

MOUSE:CSKP

enables

GO:0042043: neurexin family protein binding

ECO:0000314: direct assay evidence used in manual assertion

F

occurs_in:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:CDK5

acts_upstream_of_or_within

GO:0018107: peptidyl-threonine phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CDK5

acts_upstream_of_or_within

GO:0018105: peptidyl-serine phosphorylation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2179066
MGI:MGI:4941828

P

Seeded From UniProt

complete

MOUSE:CDK5

acts_upstream_of_or_within

GO:0035418: protein localization to synapse

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:CDK5

acts_upstream_of_or_within

GO:0032092: positive regulation of protein binding

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:4941830

P

Seeded From UniProt

complete

MOUSE:CDK5

acts_upstream_of_or_within

GO:0007416: synapse assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(EMAPA:16894)

Seeded From UniProt

complete

MOUSE:CDK5

acts_upstream_of_or_within

GO:0018105: peptidyl-serine phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CDK5

enables

GO:0004672: protein kinase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2179066
MGI:MGI:4941828

F

Seeded From UniProt

complete

MOUSE:CDK5

enables

GO:0004674: protein serine/threonine kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:CDK5

acts_upstream_of_or_within

GO:0070509: calcium ion import

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(CL:0000540)

Seeded From UniProt

complete

MOUSE:CDK5

acts_upstream_of_or_within

GO:0090314: positive regulation of protein targeting to membrane

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:4941830

P

Seeded From UniProt

complete


See also

References

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