TrkB-T1 regulates the RhoA signaling and actin cytoskeleton in glioma cells.
Recently, the truncated TrkB receptor, T1, has been reported to be involved in the control of cell morphology via the regulation of Rho proteins, through which T1 binds Rho guanine nucleotide dissociation inhibitor (Rho GDI) 1 and dissociates it in a brain-derived neurotrophic factor (BDNF)-dependent manner. However, it is unclear whether T1 signaling regulates the downstream of Rho signaling and the actin cytoskeleton. In this study, we investigated this question using C6 rat glioma cells, which express T1 endogenously. Rho GDI1 was dissociated from T1 in a BDNF-dependent manner, which also causes decreases in the activities of Rho-signaling molecules such as RhoA, Rho-associated kinase, p21-activated kinase, and extracellular-signal regulated kinase1/2. Moreover, BDNF treatment resulted in the disappearance of stress fibers in the cells treated with lysophosphatidic acid, an activator of RhoA, and in morphological changes in cells. Furthermore, a competitive assay with cyan fluorescent protein fusion proteins of T1-specific sequences reduced the effects of BDNF. These results suggest that T1 regulates the Rho-signaling pathways and the actin cytoskeleton.
Ohira
Koji
K
Department of Cellular and Molecular Biology, Primate Research Institute, Kyoto University, Aichi, Japan.
Homma
Koichi J
KJ
Hirai
Hirohisa
H
Nakamura
Shun
S
Hayashi
Motoharu
M
D000199:Actins / Q000378:metabolism*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D054462:p21-Activated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D000199:Actins; D019208:Brain-Derived Neurotrophic Factor; C086796:GDP dissociation inhibitor 1; D020730:Guanine Nucleotide Dissociation Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D020813:Receptor, trkB; C515910:Pak2 protein, rat; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D020742:rhoA GTP-Binding Protein