Role of PTB-like protein, a neuronal RNA-binding protein, during the differentiation of PC12 cells.
PTB-like protein (PTBLP) is a new homologue of pyrimidine tract binding protein (PTB), and has been cloned as a possible autoantigen in cancer-associated retinopathy. PTBLP has two functional domains, the nuclear localization signal and the RNA recognition motifs (RRMs). Full-length PTBLP (PTBLP-L) has four RRMs, and its alternative splicing product (PTBLP-S) lacks the third and fourth RRMs. Although PTBLPs are expressed in neuronal tissues, the function of PTBLPs has not been determined. We have studed whether PTBLP plays a role in neuronal differentiation using PC12 cells. During the process of nerve growth factor-induced neuronal differentiation of PC12 cells, PTBLP-L was down-regulated whereas PTBLP-S was up-regulated. Transfection of PTBLP-L into PC12 cells led to the suppression of neuronal differentiation. In PTBLP-S transfected cells, however, this suppression was not evident. When both PTBLP-L and PTBLP-S were co-transfected, the suppressive effect of PTBLP-L decreased. In differentiated cells, PTBLP-S localized in the nucleus and PTBLP-L was found dispersed throughout the cytoplasm and neuronal growth cone. These findings suggest that PTBLP-L acts as a negative regulator of neuronal differentiation and PTBLP-S acts as a competitor of PTBLP-L.
Ichikawa
Masaki
M
Department of Ophthalmology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Kikuchi
Takanobu
T
Tateiwa
Hisashi
H
Gotoh
Norimoto
N
Ohta
Kouichi
K
Arai
Jun
J
Yoshimura
Nagahisa
N
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D020932:Nerve Growth Factor / Q000494:pharmacology; D016900:Neurofilament Proteins / Q000096:biosynthesis; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D016716:PC12 Cells; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000502:physiology; D051381:Rats; D014162:Transfection
D016900:Neurofilament Proteins; D016601:RNA-Binding Proteins; D038941:Polypyrimidine Tract-Binding Protein; D020932:Nerve Growth Factor