Dysbindin-1, WAVE2 and Abi-1 form a complex that regulates dendritic spine formation.
Genetic variations in dysbindin-1 (dystrobrevin-binding protein-1) are one of the most commonly reported variations associated with schizophrenia. As schizophrenia could be regarded as a neurodevelopmental disorder resulting from abnormalities of synaptic connectivity, we attempted to clarify the function of dysbindin-1 in neuronal development. We examined the developmental change of dysbindin-1 in rat brain by western blotting and found that a 50 kDa isoform is highly expressed during the embryonic stage, whereas a 40 kDa one is detected at postnatal day 11 and increased thereafter. Immunofluorescent analyses revealed that dysbindin-1 is enriched at the spine-like structure of primary cultured rat hippocampal neurons. We identified WAVE2, but not N-WASP, as a binding partner for dysbindin-1. We also found that Abi-1, a binding molecule for WAVE2 involved in spine morphogenesis, interacts with dysbindin-1. Although dysbindin-1, WAVE2 and Abi-1 form a ternary complex, dysbindin-1 promoted the binding of WAVE2 to Abi-1. RNA interference-mediated knockdown of dysbindin-1 led to the generation of abnormally elongated immature dendritic protrusions. The present results indicate possible functions of dysbindin-1 at the postsynapse in the regulation of dendritic spine morphogenesis through the interaction with WAVE2 and Abi-1.
Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan.
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H
Ito
R
R
Morishita
T
T
Shinoda
I
I
Iwamoto
K
K
Sudo
K
K
Okamoto
K
K
Nagata
D048868:Adaptor Proteins, Signal Transducing; D000367:Age Factors; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000378:metabolism*; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D006624:Hippocampus / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D046912:Multiprotein Complexes / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D034741:RNA, Small Interfering; D051381:Rats; D012559:Schizophrenia / Q000378:metabolism* / Q000503:physiopathology; D013569:Synapses / Q000378:metabolism; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000378:metabolism
C554931:Abi1 protein, rat; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C574928:Dtnbp1 protein, rat; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; C495770:Wasl protein, rat; D051300:Wiskott-Aldrich Syndrome Protein Family; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal