Functional characterization of human NTRK2 mutations identified in patients with severe early-onset obesity

International Journal of Obesity

Volumn 31, Issue 2, 2007, Pages 359-364

  Gray, J ^a   Yeo, G ^a   Hung, C ^a   Keogh, J ^a   Clayton, P ^b   Banerjee, K ^c   McAulay, A ^d   O'Rahilly, S ^a   Farooqi, I S ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b ROYAL MANCHESTER CHILDREN S HOSPITAL   (United Kingdom)

^c WHIPPS CROSS UNIVERSITY HOSPITAL   (United Kingdom)

^d POOLE HOSPITAL NHS FOUNDATION TRUST   (United Kingdom)

Author keywords

BDNF; Neurotrophin; TrkB

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR RECEPTOR; MITOGEN ACTIVATED PROTEIN KINASE; NEUROTROPHIN; PHOSPHOLIPASE C GAMMA; PROTEIN KINASE B;

ANIMAL CELL; ARTICLE; AUTOPHOSPHORYLATION; CELL LINE; CELL LYSATE; CELL SURVIVAL; CHILD; CONTROLLED STUDY; ENZYME ACTIVATION; GENE CONSTRUCT; GENE MUTATION; GENETIC IDENTIFICATION; GENETIC TRAIT; GENETIC TRANSFECTION; GENETIC VARIABILITY; HUMAN; HYPERPHAGIA; HYPOTHALAMUS; MALE; NERVE FIBER GROWTH; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; OBESITY; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; SIGNAL TRANSDUCTION; WESTERN BLOTTING;

AGE OF ONSET; ANIMALS; BRAIN-DERIVED NEUROTROPHIC FACTOR; CELL DIVISION; CELL LINE; CELL SURVIVAL; CHILD; HUMANS; MALE; MUTATION, MISSENSE; NEURITES; OBESITY; PHOSPHORYLATION; RATS; RECEPTOR, TRKB; SIGNAL TRANSDUCTION; TRANSFECTION;

RODENTIA;

EID: 33846613209     PISSN: 03070565     EISSN: 14765497     Source Type: Journal    
DOI: 10.1038/sj.ijo.0803390     Document Type: Article

References (27)

1. O'Rahilly S, Farooqi IS, Yeo GS, Challis BG. Minireview: human obesity - lessons from monogenic disorders. Endocrinology 2003; 144: 3757-3764.
2. Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997; 387: 903-908.
3. Clement K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D et al. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 1998; 392: 398-401.
4. Krude H, Biebermann H, Luck W, Horn R, Brabant G, Gruters A. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet 1998; 19: 155-157.
5. Jackson RS, Creemers JW, Ohagi S, Raffin-Sanson ML, Sanders L, Montague CT et al. Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet 1997; 16: 303-306.
6. Yeo GS, Farooqi IS, Aminian S, Halsall DJ, Stanhope RG, O'Rahilly S. A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat Genet 1998; 20: 111-112.
7. Bouret SG, Draper SJ, Simerly RB. Trophic action of leptin on hypothalamic neurons that regulate feeding. Science 2004; 304: 108-110.
8. Pinto S, Roseberry AG, Liu H, Diano S, Shanabrough M, Cai X et al. Rapid rewiring of arcuate nucleus feeding circuits by leptin. Science 2004; 304: 110-115.
9. Kokoeva MV, Yin H, Flier JS. Neurogenesis in the hypothalamus of adult mice: potential role in energy balance. Science 2005; 310: 679-683.
10. Jones KR, Farinas I, Backus C, Reichardt LF. Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development. Cell 1994; 76: 989-999.
11. Klein R, Smeyne RJ, Wurst W, Long LK, Auerbach BA, Joyner AL et al. Targeted disruption of the TrkB neurotrophin receptor gene results in nervous system lesions and neonatal death. Cell 1993; 75: 113-122.
12. Xu B, Goulding EH, Zang K, Cepoi D, Cone RD, Jones KR et al. Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat Neurosci 2003; 6: 736-742.
13. Kernie SG, Liebl DJ, Parada LF. BDNF regulates eating behavior and locomotor activity in mice. EMBO J 2000; 19: 1290-1300.
14. Rios M, Fan G, Fekete C, Kelly J, Bates B, Kuehn R et al. Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity. Mol Endocrinol 2001; 15: 1748-1757.
15. Zorner B, Wolfer DP, Brandis D, Kretz O, Zacher C, Madani R et al. Forebrain-specific TrkB-receptor knockout mice: behaviorally more hyperactive than 'depressive'. Biol Psychiatry 2003; 54: 972-982.
16. Minichiello L, Korte M, Wolfer D, Kuhn R, Unsicker K, Cestari V et al. Essential role for TrkB receptors in hippocampus-mediated learning. Neuron 1999; 24: 401-414.
17. Linnarsson S, Bjorklund A, Ernfors P. Learning deficit in BDNF mutant mice. Eur J Neurosci 1997; 9: 2581-2587.
18. Korte M, Carroll P, Wolf E, Brem G, Thoenen H, Bonhoeffer T. Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor. Proc Natl Acad Sci USA 1995; 92: 8856-8860.
19. Monteggia LM, Barrot M, Powell CM, Berton O, Galanis V, Gemelli T et al. Essential role of brain-derived neurotrophic factor in adult hippocampal function. Proc Natl Acad Sci USA 2004; 101: 10827-10832.
20. Xu B, Gottschalk W, Chow A, Wilson RI, Schnell E, Zang K et al. The role of brain-derived neurotrophic factor receptors in the mature hippocampus: modulation of long-term potentiation through a presynaptic mechanism involving TrkB. J Neurosci 2000; 20: 6888-6897.
21. Yeo GS, Connie Hung CC, Rochford J, Keogh J, Gray J, Sivaramakrishnan S et al. A de novo mutation affecting human TrkB associated with severe obesity and developmental delay. Nat Neurosci 2004; 7: 1187-1189.
22. Iwasaki Y, Ishikawa M, Okada N, Koizumi S. Induction of a distinct morphology and signal transduction in TrkB/PC12 cells by nerve growth factor and brain-derived neurotrophic factor. J Neurochem 1997; 68: 927-934.
23. Haniu M, Montestruque S, Bures EJ, Talvenheimo J, Toso R, Lewis-Sandy S et al. Interactions between brain-derived neurotrophic factor and the TRKB receptor. Identification of two ligand binding domains in soluble TRKB by affinity separation and chemical cross-linking. J Biol Chem 1997; 272: 25296-25303.
24. Atwal JK, Massie B, Miller FD, Kaplan DR. The TrkB-Shc site signals neuronal survival and local axon growth via MEK and P13-kinase. Neuron 2000; 27: 265-277.
25. Bibel M, Barde YA. Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system. Genes Dev 2000; 14: 2919-2937.
26. Patapoutian A, Reichardt LF. Trk receptors: mediators of neurotrophin action. Curr Opin Neurobiol 2001; 11: 272-280.
27. Delmas P, Coste B. Na+ channel Nav1.9: in search of a gating mechanism. Trends Neurosci 2003; 26: 55-57.