我々はDab1が樹状突起形成に関与し核移行する事を明らかにした事から, Dab1が遺伝子発現制御を介して樹状突起形成を行う仮説を考えた。dab1ノックダウンと同時に候補分子を発現させた結果, 樹状突起が一部正常に形成された為, 候補分子がDab1の下流分子である可能性が示唆された。候補分子のタンパク質量はreelerマウスで顕著な差が無かった為, 候補分子によるDab1シグナルの増強の可能性を検討した。候補分子をノックダウン後にReelin刺激を行い, Dab1のチロシンリン酸化量を観察したが, 顕著な変化が観察されなかったことから, 他の制御機構によって樹状突起形成の制御が行われている可能性が示唆された。
As we have found that Dab1 is involved in dendrite formation and is subject to nucleocytoplamic shuttling, we hypothesized that Dab1 might regulate the dendrite formation through the regulation of gene expression. To examine this hypothesis, we expressed a candidate gene to dab1-knockdonwed neurons, and found that a candidate gene could partially rescue the abnormal dendrite formation. Because of no significant difference in Dab1 protein amount in reeler, we next examined whether the candidate molecule could enhance a putative dendrite formation signal by Dab1-signaling pathway. Dissociated neurons with or without knockdown plasmids against the candidate molecule were treated with Reelin, and Dab1 tyrosine phosphorylation, a plausible target of the candidate molecule, was compared. However, we could not detect a significant difference of the level, suggesting that the dendrite formation rescue effects by the candidate molecule might be caused by other regulation mechanism.
|
