GSKIP, an inhibitor of GSK3beta, mediates the N-cadherin/beta-catenin pool in the differentiation of SH-SY5Y cells.
Emerging evidence has shown that GSK3beta plays a pivotal role in regulating the specification of axons and dendrites. Our previous study has shown a novel GSK3beta interaction protein (GSKIP) able to negatively regulate GSK3beta in Wnt signaling pathway. To further characterize how GSKIP functions in neurons, human neuroblastoma SH-SY5Y cells treated with retinoic acid (RA) to differentiate to neuron-like cells was used as a model. Overexpression of GSKIP prevents neurite outgrowth in SH-SY5Y cells. GSKIP may affect GSK3beta activity on neurite outgrowth by inhibiting the specific phosphorylation of tau (ser396). GSKIP also increases beta-catenin in the nucleus and raises the level of cyclin D1 to promote cell-cycle progression in SH-SY5Y cells. Additionally, overexpression of GSKIP downregulates N-cadherin expression, resulting in decreased recruitment of beta-catenin. Moreover, depletion of beta-catenin by small interfering RNA, neurite outgrowth is blocked in SH-SY5Y cells. Altogether, we propose a model to show that GSKIP regulates the functional interplay of the GSK3beta/beta-catenin, beta-catenin/cyclin D1, and beta-catenin/N-cadherin pool during RA signaling in SH-SY5Y cells.
Lin
Ching-Chih
CC
Department of Biochemistry, Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
Chou
Chia-Hua
CH
Howng
Shen-Long
SL
Hsu
Chia-Yi
CY
Hwang
Chi-Ching
CC
Wang
Chihuei
C
Hsu
Ching-Mei
CM
Hong
Yi-Ren
YR
D015820:Cadherins / Q000378:metabolism*; D002453:Cell Cycle; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation; D012097:Repressor Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
D015820:Cadherins; C514503:GSKIP protein, human; D012097:Repressor Proteins; D051176:beta Catenin; D016875:tau Proteins; D019938:Cyclin D1; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3