Bcl11A/CTIP1 mediates the effect of the glutamate receptor on axon branching and dendrite outgrowth.
While neuronal activity regulates neurite outgrowth and branching, the details of the underlying mechanisms are still largely unclear. This study investigated the effect of the glutamate receptors on neuritogenesis using cultured hippocampal neurons. At 3-4 days in vitro, NMDA treatment promoted axon branching but not primary axon extension. In contrast, blockade of the NMDA receptor (NMDAR) by AP5 treatment enhanced primary axon extension. NMDAR activation also increased dendrite number and total dendrite length. These results suggest that NMDAR controls axon and dendrite morphogenesis. A previous study demonstrated that knockdown of the zinc finger transcription factor B cell lymphoma 11A-long (Bcl11A-L) reduces deleted in colorectal cancer (DCC) and microtubule-associated protein (MAP) 1b expression, thereby promoting axon branching. Here, glutamate stimulation down-regulated the levels of the Bcl11A-L, DCC, MAP1b, and MAP2c proteins. Over-expression of either Bcl11A-L or DCC countered the effect of NMDA or glutamate on axon branching and dendrite outgrowth, indicating that the Bcl11A-L/DCC pathway is an important downstream effector of glutamate receptors in neurite arborization. Because knockdown of Bcl11A-L did not down-regulate MAP2c, our results suggest that glutamate receptors also use a Bcl11A-L-independent pathway to control dendrite outgrowth. To summarize, this study reveals novel pathways downstream of glutamate receptors that regulate axon and dendrite arborization.
The Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
Ting-Yu
TY
Kuo
Chiung-Ya
CY
Chen
Yi-Ping
YP
Hsueh
D000818:Animals; D001369:Axons / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology*; D049108:Cell Enlargement; D002478:Cells, Cultured; D000075389:DCC Receptor; D003712:Dendrites / Q000502:physiology*; D018698:Glutamic Acid / Q000494:pharmacology; D016202:N-Methylaspartate / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology*; D012097:Repressor Proteins; D015398:Signal Transduction / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000502:physiology; D016335:Zinc Fingers / Q000502:physiology*
C486563:BCL11A protein, human; D002352:Carrier Proteins; D000075389:DCC Receptor; C501912:Dcc protein, rat; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; D017470:Receptors, Glutamate; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D018698:Glutamic Acid; D016202:N-Methylaspartate