title: Regulation of dendritic arborization by BCR Rac1 GTPase-activating protein, a substrate of PTPRT.
abstract: Dendritic arborization is important for neuronal development as well as the formation of neural circuits. Rac1 is a member of the Rho GTPase family that serve as regulators of neuronal development. Breakpoint cluster region protein (BCR) is a Rac1 GTPase-activating protein that is abundantly expressed in the central nervous system. Here, we show that BCR plays a key role in neuronal development. Dendritic arborization and actin polymerization were attenuated by overexpression of BCR in hippocampal neurons. Knockdown of BCR using specific shRNAs increased the dendritic arborization as well as actin polymerization. The number of dendrites in null mutant BCR(-/-) mice was considerably increased compared with that in wild-type mice. We found that the function of the BCR GTPase-activating domain could be modulated by protein tyrosine phosphatase receptor T (PTPRT), which is expressed principally in the brain. We demonstrate that tyrosine 177 of BCR was the main target of PTPRT and the BCR mutant mimicking dephosphorylation of tyrosine 177 alleviated the attenuation of dendritic arborization. Additionally the attenuated dendritic arborization found upon BCR overexpression was relieved upon co-expression of PTPRT. When PTPRT was knocked down by a specific shRNA, the dendritic arborization was significantly reduced. The activity of the BCR GTPase-activating domain was modulated by means of conversions between the intra- and inter-molecular interactions, which are finely regulated through the dephosphorylation of a specific tyrosine residue by PTPRT. We thus show conclusively that BCR is a novel substrate of PTPRT and that BCR is involved in the regulation of neuronal development via control of the BCR GTPase-activating domain function by PTPRT.
authors: Biomedical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806,  Korea.
authors: A-Reum
authors: AR
authors: Park
authors: Daeyoung
authors: D
authors: Oh
authors: So-Hee
authors: SH
authors: Lim
authors: Jeonghoon
authors: J
authors: Choi
authors: Jeonghee
authors: J
authors: Moon
authors: Dae-Yeol
authors: DY
authors: Yu
authors: Sung Goo
authors: SG
authors: Park
authors: Nora
authors: N
authors: Heisterkamp
authors: Eunjoon
authors: E
authors: Kim
authors: Pyung-Keun
authors: PK
authors: Myung
authors: Jae-Ran
authors: JR
authors: Lee
mesh_terms: D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D003712:Dendrites / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D058105:Polymerization; D017434:Protein Structure, Tertiary; D051562:Proto-Oncogene Proteins c-bcr / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D051381:Rats; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000378:metabolism*; D017384:Sequence Deletion; D015398:Signal Transduction; D013379:Substrate Specificity; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; D020690:GTPase-Activating Proteins; D019000:Phosphotyrosine; D051562:Proto-Oncogene Proteins c-bcr; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D020830:rac1 GTP-Binding Protein