Sez-6 proteins affect dendritic arborization patterns and excitability of cortical pyramidal neurons.
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.
Gunnersen
Jenny M
JM
Brain Development Laboratory, Howard Florey Institute, The University of Melbourne, Parkville, Victoria, 3010, Australia. jenny.gunnersen@florey.edu.au
Kim
Mary H
MH
Fuller
Stephanie J
SJ
De Silva
Melanie
M
Britto
Joanne M
JM
Hammond
Vicki E
VE
Davies
Philip J
PJ
Petrou
Steve
S
Faber
E S Louise
ES
Sah
Pankaj
P
Tan
Seong-Seng
SS
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000166:cytology* / Q000378:metabolism; D003072:Cognition Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure*; D049229:Dendritic Spines / Q000378:metabolism / Q000648:ultrastructure; D000076122:Disks Large Homolog 4 Protein; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009421:Nervous System Malformations / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009434:Neural Pathways / Q000002:abnormalities / Q000166:cytology / Q000378:metabolism; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000166:cytology* / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics
D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C093131:Sez6 protein, mouse; D051528:Guanylate Kinases