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PMID:18031681

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Citation

Gunnersen, JM, Kim, MH, Fuller, SJ, De Silva, M, Britto, JM, Hammond, VE, Davies, PJ, Petrou, S, Faber, ES, Sah, P and Tan, SS (2007) Sez-6 proteins affect dendritic arborization patterns and excitability of cortical pyramidal neurons. Neuron 56:621-39

Abstract

Development of appropriate dendritic arbors is crucial for neuronal information transfer. We show, using seizure-related gene 6 (sez-6) null mutant mice, that Sez-6 is required for normal dendritic arborization of cortical neurons. Deep-layer pyramidal neurons in the somatosensory cortex of sez-6 null mice exhibit an excess of short dendrites, and cultured cortical neurons lacking Sez-6 display excessive neurite branching. Overexpression of individual Sez-6 isoforms in knockout neurons reveals opposing actions of membrane-bound and secreted Sez-6 proteins, with membrane-bound Sez-6 exerting an antibranching effect under both basal and depolarizing conditions. Layer V pyramidal neurons in knockout brain slices show reduced excitatory postsynaptic responses and a reduced dendritic spine density, reflected by diminished punctate staining for postsynaptic density 95 (PSD-95). In behavioral tests, the sez-6 null mice display specific exploratory, motor, and cognitive deficits. In conclusion, cell-surface protein complexes involving Sez-6 help to sculpt the dendritic arbor, in turn enhancing synaptic connectivity.

Links

PubMed Online version:10.1016/j.neuron.2007.09.018

Keywords

Animals; Cell Differentiation/genetics; Cell Membrane/genetics; Cell Membrane/metabolism; Cells, Cultured; Cerebral Cortex/abnormalities; Cerebral Cortex/cytology; Cerebral Cortex/metabolism; Cognition Disorders/genetics; Cognition Disorders/metabolism; Cognition Disorders/physiopathology; Dendrites/metabolism; Dendrites/ultrastructure; Dendritic Spines/metabolism; Dendritic Spines/ultrastructure; Excitatory Postsynaptic Potentials/genetics; Female; Gene Expression Regulation, Developmental/genetics; Guanylate Kinase; Intracellular Signaling Peptides and Proteins/metabolism; Male; Membrane Proteins/metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Nerve Tissue Proteins/genetics; Nervous System Malformations/genetics; Nervous System Malformations/metabolism; Nervous System Malformations/physiopathology; Neural Pathways/abnormalities; Neural Pathways/cytology; Neural Pathways/metabolism; Organ Culture Techniques; Patch-Clamp Techniques; Pyramidal Cells/cytology; Pyramidal Cells/metabolism; Synaptic Transmission/genetics

Significance

Annotations

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

MOUSE:SEZ6

located_in

GO:0043197: dendritic spine

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SEZ6

located_in

GO:0043198: dendritic shaft

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SEZ6

located_in

GO:0097440: apical dendrite

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000561)
  • part_of:(EMAPA:17168)

Seeded From UniProt

complete

MOUSE:SEZ6

acts_upstream_of_or_within

GO:0050773: regulation of dendrite development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3777582

P

Seeded From UniProt

complete

MOUSE:SEZ6

acts_upstream_of_or_within

GO:0060079: excitatory postsynaptic potential

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3777582

P

  • occurs_in:(CL:0000598)
  • occurs_in:(EMAPA:36597)|occurs_in:(CL:0000598)
  • occurs_in:(EMAPA:36597)|occurs_in:(CL:0000598)
  • occurs_in:(EMAPA:36597)|occurs_in:(CL:0000598)
  • occurs_in:(EMAPA:36597)

Seeded From UniProt

complete


See also

References

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