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Titolo:
Overexpression of HuD, but not of its truncated form HuD I+II, promotes GAP-43 gene expression and neurite outgrowth in PC12 cells in the absence of nerve growth factor
Autore:
Anderson, KD; Morin, MA; Beckel-Mitchener, A; Mobarak, CD; Neve, RL; Furneaux, HM; Burry, R; Perrone-Bizzozero, NI;
Indirizzi:
Univ New Mexico, Sch Med, Dept Neurosci, Albuquerque, NM 87131 USA Univ New Mexico Albuquerque NM USA 87131 rosci, Albuquerque, NM 87131 USA McLean Hosp, Belmont, MA 02178 USA McLean Hosp Belmont MA USA 02178McLean Hosp, Belmont, MA 02178 USA Harvard Univ, Sch Med, Dept Genet, Belmont, MA 02178 USA Harvard Univ Belmont MA USA 02178 Med, Dept Genet, Belmont, MA 02178 USA Sloan Kettering Canc Inst, Program Mol Pharmacol & Therapeut, New York, NYUSA Sloan Kettering Canc Inst New York NY USA l & Therapeut, New York, NYUSA Ohio State Univ, Dept Cell Biol Neurobiol & Anat, Columbus, OH 43210 USA Ohio State Univ Columbus OH USA 43210 biol & Anat, Columbus, OH 43210 USA
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 3, volume: 75, anno: 2000,
pagine: 1103 - 1114
SICI:
0022-3042(200009)75:3<1103:OOHBNO>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
RNA-BINDING PROTEIN; MESSENGER-RNA; 3'-UNTRANSLATED REGION; DROSOPHILA-MELANOGASTER; NEURONAL DEVELOPMENT; TRANSGENIC MICE; LUNG-CARCINOMA; AXONAL GROWTH; IN-VITRO; ELAV;
Keywords:
growth-associated protein-43; neurite outgrowth; Hu proteins; PC12 cells; mRNA stability;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
68
Recensione:
Indirizzi per estratti:
Indirizzo: Perrone-Bizzozero, NI Univ New Mexico, Sch Med, Dept Neurosci, Albuquerque, NM 87131 USA Univ New Mexico Albuquerque NM USA 87131 87131 USA
Citazione:
K.D. Anderson et al., "Overexpression of HuD, but not of its truncated form HuD I+II, promotes GAP-43 gene expression and neurite outgrowth in PC12 cells in the absence of nerve growth factor", J NEUROCHEM, 75(3), 2000, pp. 1103-1114

Abstract

We have previously shown that the RNA-binding protein HuD binds to a regulatory element in the growth-associated protein (GAP)-43 mRNA and that this interaction involves its first two RNA recognition motifs (RRMs). In this study, we investigated the functional significance of this interaction by overexpression of human HuD protein (pcHuD) or its truncated form lacking thethird RRM (pcHuD I+II) in PC12 cells. Morphological analysis revealed thatpcHuD cells extended short neurites containing GAP-43-positive growth cones in the absence of nerve growth factor (NGF). These processes also contained tubulin and F-actin filaments but were not stained with antibodies against neurofilament M protein. In correlation with this phenotype, pcHuD cellscontained higher levels of GAP-43 without changes in levels of other NGF-induced proteins, such as SNAP-25 and tau, In mRNA decay studies, HuD stabilized the GAP-43 mRNA, whereas HuD I+II did not have any effect either on GAP-43 mRNA stability or on the levels of GAP-43 protein. Likewise, pcHuD I+II cells showed no spontaneous neurite outgrowth and deficient outgrowth in response to NGF, Our results indicate that HuD is sufficient to increase GAP-43 gene expression and neurite outgrowth in the absence of NGF and that the third RRM in the protein is critical for this function.

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Documento generato il 12/07/20 alle ore 08:55:20