Emerging major synaptic signaling pathways involved in intellectual disability

Molecular Psychiatry

Volumn 17, Issue 7, 2012, Pages 682-693

  Pavlowsky, A ^a,b,c,d   Chelly, J ^a,b   Billuart, P ^a,b  

^a INSTITUT COCHIN   (France)

^b INSERM   (France)

^c SUNY DOWNSTATE MEDICAL CENTER   (United States)

^d SUNY Downstate Medical Center   (United States)

Author keywords

genetic; mental retardation; signaling pathways; synapse

Indexed keywords

ARF PROTEIN; CELL PROTEIN; INTERLEUKIN 1 RECEPTOR; INTERLEUKIN 1 RECEPTOR ACCESSORY PROTEIN LIKE 1; JANUS KINASE; MITOGEN ACTIVATED PROTEIN KINASE; POSTSYNAPTIC DENSITY PROTEIN 95; PROTEIN SAP102; PROTEIN SYNGAP; RAB PROTEIN; RAS PROTEIN; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; UNCLASSIFIED DRUG;

COGNITIVE DEFECT; GENE FUNCTION; GENE PRODUCT; HUMAN; INTELLECTUAL IMPAIRMENT; MORPHOGENESIS; NERVE CELL PLASTICITY; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; REVIEW; SYNAPTIC POTENTIAL;

ANIMALS; DENDRITIC SPINES; HUMANS; INTELLECTUAL DISABILITY; MAP KINASE SIGNALING SYSTEM; MODELS, NEUROLOGICAL; MONOMERIC GTP-BINDING PROTEINS; NEURONAL PLASTICITY; SIGNAL TRANSDUCTION; SYNAPTIC TRANSMISSION;

EID: 84862762284     PISSN: 13594184     EISSN: 14765578     Source Type: Journal    
DOI: 10.1038/mp.2011.139     Document Type: Review

References (115)

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Washington, DC, 2000.
2. Chelly J, Khelfaoui M, Francis F, Cherif B, Bienvenu T. Genetics and pathophysiology of mental retardation. Eur J Hum Genet 2006; 14: 701-713. (Pubitemid 43797267)
3. Humeau Y, Gambino F, Chelly J, Vitale N. X-linked mental retardation: focus on synaptic function and plasticity. J Neurochem 2009; 109: 1-14.
4. Vaillend C, Poirier R, Laroche S. Genes, plasticity and mental retardation. Behav Brain Res 2008; 192: 88-105.
5. Purpura DP. Dendritic spine 'dysgenesis' and mental retardation. Science 1974; 186: 1126-1128.
6. Ramakers GJ. Rho proteins, mental retardation and the cellular basis of cognition. Trends Neurosci 2002; 25: 191-199. (Pubitemid 34615536)
7. Fiala JC, Spacek J, Harris KM. Dendritic spine pathology: cause or consequence of neurological disorders? Brain Res Rev 2002; 39: 29-54. (Pubitemid 34666985)
8. Yoshihara Y, De Roo M, Muller D. Dendritic spine formation and stabilization. Curr Opin Neurobiol 2009; 19: 146-153.
9. Matozaki T, Nakanishi H, Takai Y. Small G-protein networks: their crosstalk and signal cascades. Cell Signal 2000; 12: 515-524.
10. Bergmann C, Zerres K, Senderek J, Rudnik-Schoneborn S, Eggermann T, Hausler M et al. Oligophrenin 1 (OPHN1) gene mutation causes syndromic X-linked mental retardation with epilepsy, rostral ventricular enlargement and cerebellar hypoplasia. Brain 2003; 126(Part 7): 1537-1544. (Pubitemid 36834930)
11. Billuart P, Bienvenu T, Ronce N, des Portes V, Vinet MC, Zemni R et al. Oligophrenin-1 encodes a rhoGAP protein involved in Xlinked mental retardation. Nature 1998; 392: 923-926. (Pubitemid 28232063)
12. Philip N, Chabrol B, Lossi AM, Cardoso C, Guerrini R, Dobyns WB et al. Mutations in the oligophrenin-1 gene (OPHN1) cause X linked congenital cerebellar hypoplasia. J Med Genet 2003; 40: 441-446. (Pubitemid 36760662)
13. Zanni G, Saillour Y, Nagara M, Billuart P, Castelnau L, Moraine C et al. Oligophrenin 1 mutations frequently cause X-linked mental retardation with cerebellar hypoplasia. Neurology 2005; 65: 1364-1369. (Pubitemid 41552762)
14. Chabrol B, Girard N, N'Guyen K, Gérard A, Carlier M, Villard L et al. Delineation of the clinical phenotype associated with OPHN1 mutations based on the clinical and neuropsychological evaluation of three families. Am j med genet 2005; 138: 314-317. (Pubitemid 41532947)
15. Bedeschi MF, Novelli A, Bernardini L, Parazzini C, Bianchi V, Torres B et al. Association of syndromic mental retardation with an Xq12q13.1 duplication encompassing the oligophrenin 1 gene. Am j med genet 2008; 146A: 1718-1724. (Pubitemid 351975483)
16. Govek EE, Newey SE, Van Aelst L. The role of the Rho GTPases in neuronal development. Genes Dev 2005; 19: 1-49. (Pubitemid 40095815)
17. Tashiro A, Yuste R. Regulation of dendritic spine motility and stability by Rac1 and Rho kinase: evidence for two forms of spine motility. Mol Cell Neurosci 2004; 26: 429-440. (Pubitemid 38968436)
18. Khelfaoui M, Denis C, van Galen E, de Bock F, Schmitt A, Houbron C et al. Loss of X-linked mental retardation gene oligophrenin1 in mice impairs spatial memory and leads to ventricular enlargement and dendritic spine immaturity. J Neurosci 2007; 27: 9439-9450. (Pubitemid 47358207)
19. Govek EE, Newey SE, Akerman CJ, Cross JR, Van der Veken L, Van Aelst L. The X-linked mental retardation protein oligophrenin-1 is required for dendritic spine morphogenesis. Nat Neurosci 2004; 7: 364-372. (Pubitemid 38429176)
20. Nadif Kasri N, Nakano-Kobayashi A, Malinow R, Li B, Van Aelst L. The Rho-linked mental retardation protein oligophrenin-1 controls synapse maturation and plasticity by stabilizing AMPA receptors. Genes Dev 2009; 23: 1289-1302.
21. Khelfaoui M, Pavlowsky A, Powell AD, Valnegri P, Cheong KW, Blandin Y et al. Inhibition of RhoA pathway rescues the endocytosis defects in Oligophrenin1 mouse model of mental retardation. Hum mol genet 2009; 18: 2575-2583.
22. Nakano-Kobayashi A, Kasri NN, Newey SE, Van Aelst L. The Rho-linked mental retardation protein OPHN1 controls synaptic vesicle endocytosis via endophilin A1. Curr Biol 2009; 19: 1133-1139.
23. Slepnev VI, De Camilli P. Accessory factors in clathrin-dependent synaptic vesicle endocytosis. Nat Rev Neurosci 2000; 1: 161-172.
24. Endris V, Wogatzky B, Leimer U, Bartsch D, Zatyka M, Latif F et al. The novel Rho-GTPase activating gene MEGAP/srGAP3 has a putative role in severe mental retardation. P Natl Acad Sci USA 2002; 99: 11754-11759. (Pubitemid 34994471)
25. Hamdan FF, Gauthier J, Pellerin S, Dobrzeniecka S, Marineau C, Fombonne E et al. No association between SRGAP3/MEGAP haploinsufficiency and mental retardation. Arch Neurol 2009; 66: 675-676.
26. Carlson BR, Lloyd KE, Kruszewski A, Kim IH, Rodriguiz RM, Heindel C et al. WRP/srGAP3 facilitates the initiation of spine development by an inverse F-BAR domain, and its loss impairs long-term memory. J Neurosci 2011; 31: 2447-2460.
27. Soderling SH, Guire ES, Kaech S, White J, Zhang F, Schutz K et al. A WAVE-1 and WRP signaling complex regulates spine density, synaptic plasticity, and memory. J Neurosci 2007; 27: 355-365. (Pubitemid 46106009)
28. Orrico A, Galli L, Faivre L, Clayton-Smith J, Azzarello-Burri SM, Hertz JM et al. Aarskog-Scott syndrome: clinical update and report of nine novel mutations of the FGD1 gene. Am j med genet 2010; 152A: 313-318.
29. Pasteris NG, Cadle A, Logie LJ, Porteous ME, Schwartz CE, Stevenson RE et al. Isolation and characterization of the faciogenital dysplasia (Aarskog-Scott syndrome) gene: a putative Rho/Rac guanine nucleotide exchange factor. Cell 1994; 79: 669-678.
30. Lebel RR, May M, Pouls S, Lubs HA, Stevenson RE, Schwartz CE. Non-syndromic X-linked mental retardation associated with a missense mutation (P312L) in the FGD1 gene. Clin Genet 2002; 61: 139-145. (Pubitemid 36372619)
31. Shimojima K, Sugawara M, Shichiji M, Mukaida S, Takayama R, Imai K et al. Loss-of-function mutation of collybistin is responsible for X-linked mental retardation associated with epilepsy. J Hum Genet 2011; 56: 561-565.
32. Harvey K, Duguid IC, Alldred MJ, Beatty SE, Ward H, Keep NH et al. The GDP-GTP exchange factor collybistin: an essential determinant of neuronal gephyrin clustering. J Neurosci 2004; 24: 5816-5826. (Pubitemid 38857236)
33. Papadopoulos T, Korte M, Eulenburg V, Kubota H, Retiounskaia M, Harvey RJ et al. Impaired GABAergic transmission and altered hippocampal synaptic plasticity in collybistin-deficient mice. EMBO J 2007; 26: 3888-3899. (Pubitemid 47367488)
34. Jedlicka P, Papadopoulos T, Deller T, Betz H, Schwarzacher SW. Increased network excitability and impaired induction of longterm potentiation in the dentate gyrus of collybistin-deficient mice in vivo. Mol Cell Neurosci 2009; 41: 94-100.
35. Reddy-Alla S, Schmitt B, Birkenfeld J, Eulenburg V, Dutertre S, Bohringer C et al. PH-domain-driven targeting of collybistin but not Cdc42 activation is required for synaptic gephyrin clustering. Eur J Neurosci 2010; 31: 1173-1184.
36. Poulopoulos A, Aramuni G, Meyer G, Soykan T, Hoon M, Papadopoulos T et al. Neuroligin 2 drives postsynaptic assembly at perisomatic inhibitory synapses through gephyrin and collybistin. Neuron 2009; 63: 628-642.
37. Kutsche K, Yntema H, Brandt A, Jantke I, Nothwang HG, Orth U et al. Mutations in ARHGEF6, encoding a guanine nucleotide exchange factor for Rho GTPases, in patients with X-linked mental retardation. Nat genet 2000; 26: 247-250.
38. Missy K, Hu B, Schilling K, Harenberg A, Sakk V, Kuchenbecker K et al. AlphaPIX Rho GTPase guanine nucleotide exchange factor regulates lymphocyte functions and antigen receptor signaling. Mol cell biol 2008; 28: 3776-3789. (Pubitemid 351732912)
39. Allen KM, Gleeson JG, Bagrodia S, Partington MW, MacMillan JC, Cerione RA et al. PAK3 mutation in nonsyndromic X-linked mental retardation. Nat genet 1998; 20: 25-30. (Pubitemid 28410338)
40. Bienvenu T, des Portes V, McDonell N, Carrie A, Zemni R, Couvert P et al. Missense mutation in PAK3, R67C, causes X-linked nonspecific mental retardation. Am J Med Genet 2000; 93: 294-298. (Pubitemid 30497449)
41. Gedeon AK, Nelson J, Gecz J, Mulley JC. X-linked mild nonsyndromic mental retardation with neuropsychiatric problems and the missense mutation A365E in PAK3. Am j med genet 2003; 120A: 509-517. (Pubitemid 37063747)
42. Peippo M, Koivisto AM, Sarkamo T, Sipponen M, von Koskull H, Ylisaukko-oja T et al. PAK3 related mental disability: further characterization of the phenotype. Am j med genet 2007; 143A: 2406-2416. (Pubitemid 47511932)
43. Scott RW, Olson MF. LIM kinases: function, regulation and association with human disease. J Mol Med 2007; 85: 555-568. (Pubitemid 46870893)
44. Arber S, Barbayannis FA, Hanser H, Schneider C, Stanyon CA, Bernard O et al. Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase. Nature 1998; 393: 805-809. (Pubitemid 28299494)
45. Hayashi ML, Choi SY, Rao BS, Jung HY, Lee HK, Zhang D et al. Altered cortical synaptic morphology and impaired memory consolidation in forebrain-specific dominant-negative PAK transgenic mice. Neuron 2004; 42: 773-787. (Pubitemid 38748791)
46. Boda B, Alberi S, Nikonenko I, Node-Langlois R, Jourdain P, Moosmayer M et al. The mental retardation protein PAK3 contributes to synapse formation and plasticity in hippocampus. J Neurosci 2004; 24: 10816-10825. (Pubitemid 39602393)
47. Kreis P, Thevenot E, Rousseau V, Boda B, Muller D, Barnier JV. The p21-activated kinase 3 implicated in mental retardation regulates spine morphogenesis through a Cdc42-dependent pathway. J Biol Chem 2007; 282: 21497-21506. (Pubitemid 47099969)
48. Meng Y, Zhang Y, Tregoubov V, Janus C, Cruz L, Jackson M et al. Abnormal spine morphology and enhanced LTP in LIMK-1 knockout mice. Neuron 2002; 35: 121-133. (Pubitemid 34804327)
49. Meng J, Meng Y, Hanna A, Janus C, Jia Z. Abnormal long-lasting synaptic plasticity and cognition in mice lacking the mental retardation gene Pak3. J Neurosci 2005; 25: 6641-6650. (Pubitemid 40995296)
50. Node-Langlois R, Muller D, Boda B. Sequential implication of the mental retardation proteins ARHGEF6 and PAK3 in spine morphogenesis. J Cell Sci 2006; 119(Part 23): 4986-4993. (Pubitemid 46017811)
51. Hamdan FF, Gauthier J, Spiegelman D, Noreau A, Yang Y, Pellerin S et al. Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation. N Engl J Med 2009; 360: 599-605.
52. Kim JH, Liao D, Lau LF, Huganir RL. SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family. Neuron 1998; 20: 683-691. (Pubitemid 28199048)
53. Tarpey P, Parnau J, Blow M, Woffendin H, Bignell G, Cox C et al. Mutations in the DLG3 gene cause nonsyndromic X-linked mental retardation. Am J Hum Genet 2004; 75: 318-324. (Pubitemid 38943875)
54. Sheng M, Sala C. PDZ domains and the organization of supramolecular complexes. Annu rev neurosci 2001; 24: 1-29. (Pubitemid 32695221)
55. Zanni G, van Esch H, Bensalem A, Saillour Y, Poirier K, Castelnau L et al. A novel mutation in the DLG3 gene encoding the synapse-associated protein 102 (SAP102) causes non-syndromic mental retardation. Neurogenetics 2010; 11: 251-255.
56. Cuthbert PC, Stanford LE, Coba MP, Ainge JA, Fink AE, Opazo P et al. Synapse-associated protein 102/dlgh3 couples the NMDA receptor to specific plasticity pathways and learning strategies. J Neurosci 2007; 27: 2673-2682. (Pubitemid 46393587)
57. Kim JH, Lee HK, Takamiya K, Huganir RL. The role of synaptic GTPase-activating protein in neuronal development and synaptic plasticity. J Neurosci 2003; 23: 1119-1124. (Pubitemid 36258890)
58. Komiyama NH,Watabe AM, Carlisle HJ, Porter K, Charlesworth P, Monti J et al. SynGAP regulates ERK/MAPK signaling, synaptic plasticity, and learning in the complex with postsynaptic density 95 and NMDA receptor. J Neurosci 2002; 22: 9721-9732. (Pubitemid 35332855)
59. Vazquez LE, Chen HJ, Sokolova I, Knuesel I, Kennedy MB. SynGAP regulates spine formation. J Neurosci 2004; 24: 8862-8872. (Pubitemid 39362982)
60. Qin Y, Zhu Y, Baumgart JP, Stornetta RL, Seidenman K, Mack V et al. State-dependent Ras signaling and AMPA receptor trafficking. Genes Dev 2005; 19: 2000-2015. (Pubitemid 41247958)
61. Carlisle HJ, Manzerra P, Marcora E, Kennedy MB. SynGAP regulates steady-state and activity-dependent phosphorylation of cofilin. J Neurosci 2008; 28: 13673-13683.
62. Kim MJ, Dunah AW, Wang YT, Sheng M. Differential roles of NR2A-and NR2B-containing NMDA receptors in Ras-ERK signaling and AMPA receptor trafficking. Neuron 2005; 46: 745-760. (Pubitemid 40733130)
63. Sans N, Petralia RS, Wang YX, Blahos II J, Hell JW, Wenthold RJ. A developmental change in NMDA receptor-associated proteins at hippocampal synapses. J Neurosci 2000; 20: 1260-1271. (Pubitemid 30220482)
64. Trivier E, De Cesare D, Jacquot S, Pannetier S, Zackai E, Young I et al. Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome. Nature 1996; 384: 567-570. (Pubitemid 26415934)
65. Sassone-Corsi P, Mizzen CA, Cheung P, Crosio C, Monaco L, Jacquot S et al. Requirement of Rsk-2 for epidermal growth factor-activated phosphorylation of histone H3. Science 1999; 285: 886-891. (Pubitemid 29381988)
66. Xing J, Ginty DD, Greenberg ME. Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase. Science 1996; 273: 959-963. (Pubitemid 26275173)
67. Pereira PM, Schneider A, Pannetier S, Heron D, Hanauer A. Coffin-Lowry syndrome. Eur J Hum Genet 2010; 18: 627-633.
68. Poirier R, Jacquot S, Vaillend C, Soutthiphong AA, Libbey M, Davis S et al. Deletion of the Coffin-Lowry syndrome gene Rsk2 in mice is associated with impaired spatial learning and reduced control of exploratory behavior. Behav Genet 2007; 37: 31-50. (Pubitemid 46144051)
69. Mehmood T, Schneider A, Sibille J, Marques Pereira P, Pannetier S, Ammar MR et al. Transcriptome profile reveals AMPA receptor dysfunction in the hippocampus of the Rsk2-knockout mice, an animal model of Coffin-Lowry syndrome. Hum Genet 2011; 129: 255-269.
70. Zeniou-Meyer M, Begle A, Bader MF, Vitale N. The Coffin-Lowry syndrome-associated protein RSK2 controls neuroendocrine secretion through the regulation of phospholipase D1 at the exocytotic sites. Ann N Y Acad Sci 2009; 1152: 201-208.
71. Zeniou-Meyer M, Liu Y, Begle A, Olanich ME, Hanauer A, Becherer U et al. The Coffin-Lowry syndrome-associated protein RSK2 is implicated in calcium-regulated exocytosis through the regulation of PLD1. P Natl Acad Sci USA 2008; 105: 8434-8439. (Pubitemid 351904774)
72. D'Adamo P, Menegon A, Lo Nigro C, Grasso M, Gulisano M, Tamanini F et al. Mutations in GDI1 are responsible for X-linked non-specific mental retardation. Nature genetics 1998; 19: 134-139. (Pubitemid 28248793)
73. Giannandrea M, Bianchi V, Mignogna ML, Sirri A, Carrabino S, D'Elia E et al. Mutations in the small GTPase gene RAB39B are responsible for X-linked mental retardation associated with autism, epilepsy, and macrocephaly. Am J Hum Genet 2010; 86: 185-195.
74. Corbett MA, Bahlo M, Jolly L, Afawi Z, Gardner AE, Oliver KL et al. A focal epilepsy and intellectual disability syndrome is due to a mutation in TBC1D24. Am J Hum Genet 2010; 87: 371-375.
75. Falace A, Filipello F, La Padula V, Vanni N, Madia F, De Pietri Tonelli D et al. TBC1D24, an ARF6-interacting protein, is mutated in familial infantile myoclonic epilepsy. Am J Hum Genet 2010; 87: 365-370.
76. Bianchi V, Farisello P, Baldelli P, Meskenaite V, Milanese M, Vecellio M et al. Cognitive impairment in Gdi1-deficient mice is associated with altered synaptic vesicle pools and short-term synaptic plasticity, and can be corrected by appropriate learning training. Hum Mol Genet 2009; 18: 105-117.
77. Donaldson JG. Multiple roles for Arf6: sorting, structuring, and signaling at the plasma membrane. J Biol Chem 2003; 278: 41573-41576. (Pubitemid 37310409)
78. D'Souza-Schorey C, Chavrier P. ARF proteins: roles in membrane traffic and beyond. Nat Rev Mol Cell Biol 2006; 7: 347-358.
79. Funakoshi Y, Hasegawa H, Kanaho Y. Regulation of PIP5K activity by Arf6 and its physiological significance. J Cell Physiol 2011; 226: 888-895.
80. Jaworski J. ARF6 in the nervous system. Eur J Cell Biol 2007; 86: 513-524. (Pubitemid 47233377)
81. Scholz R, Berberich S, Rathgeber L, Kolleker A, Kohr G, Kornau HC. AMPA receptor signaling through BRAG2 and Arf6 critical for long-term synaptic depression. Neuron 2010; 66: 768-780.
82. Sanda M, Kamata A, Katsumata O, Fukunaga K, Watanabe M, Kondo H et al. The postsynaptic density protein, IQ-ArfGEF/BRAG1, can interact with IRSp53 through its proline-rich sequence. Brain Res 2009; 1251: 7-15.
83. Sakagami H, Sanda M, Fukaya M, Miyazaki T, Sukegawa J, Yanagisawa T et al. IQ-ArfGEF/BRAG1 is a guanine nucleotide exchange factor for Arf6 that interacts with PSD-95 at postsynaptic density of excitatory synapses. Neurosci Res 2008; 60: 199-212.
84. Shoubridge C, Tarpey PS, Abidi F, Ramsden SL, Rujirabanjerd S, Murphy JA et al. Mutations in the guanine nucleotide exchange factor gene IQSEC2 cause nonsyndromic intellectual disability. Nat genet 2010; 42: 486-488.
85. Shoubridge C, Walikonis RS, Gecz J, Harvey RJ. Subtle functional defects in the Arf-specific guanine nucleotide exchange factor IQSEC2 cause non-syndromic X-linked intellectual disability. Small Gtpases 2010; 1: 98-103.
86. Carrie A, Jun L, Bienvenu T, Vinet MC, McDonell N, Couvert P et al. A new member of the IL-1 receptor family highly expressed in hippocampus and involved in X-linked mental retardation. Nat genet 1999; 23: 25-31. (Pubitemid 29418783)
87. Bahi N, Friocourt G, Carrie A, Graham ME, Weiss JL, Chafey P et al. IL1 receptor accessory protein like, a protein involved in Xlinked mental retardation, interacts with Neuronal Calcium Sensor-1 and regulates exocytosis. Hum Mol Genet 2003; 12: 1415-1425. (Pubitemid 36758454)
88. Pavlowsky A, Gianfelice A, Pallotto M, Zanchi A, Vara H, Khelfaoui M et al. A postsynaptic signaling pathway that may account for the cognitive defect due to IL1RAPL1 mutation. Curr Biol 2010; 20: 103-115.
89. Piton A, Michaud J, Peng H, Aradhya S, Gauthier J, Mottron L et al. Mutations in the calcium-related gene IL1RAPL1 are associated with autism. Hum Mol Genet 2008; 17: 3965-3974. (Pubitemid 352762857)
90. Nawara M, Klapecki J, Borg K, Jurek M, Moreno S, Tryfon J et al. Novel mutation of IL1RAPL1gene in a nonspecific X-linked mental retardation (MRX) family. Am J Med Genet 2008; 146A: 3167-3172.
91. Tabolacci E, Pomponi MG, Pietrobono R, Terracciano A, Chiurazzi P, Neri G. A truncating mutation in the IL1RAPL1 gene is responsible for X-linked mental retardation in the MRX21 family. Am j med genet 2006; 140: 482-487. (Pubitemid 43376320)
92. Gambino F, Pavlowsky A, Begle A, Dupont JL, Bahi N, Courjaret R et al. IL1-receptor accessory protein-like 1 (IL1RAPL1), a protein involved in cognitive functions, regulates N-type Ca2+-channel and neurite elongation. P Natl Acad Sci USA 2007; 104: 9063-9068. (Pubitemid 47175437)
93. Handley MT, Lian LY, Haynes LP, Burgoyne RD. Structural and functional deficits in a neuronal calcium sensor-1 mutant identified in a case of autistic spectrum disorder. PLoS One 2010; 5: e10534.
94. Kim MJ, Futai K, Jo J, Hayashi Y, Cho K, Sheng M. Synaptic accumulation of PSD-95 and synaptic function regulated by phosphorylation of serine-295 of PSD-95. Neuron 2007; 56: 488-502. (Pubitemid 350026266)
95. Born TL, Smith DE, Garka KE, Renshaw BR, Bertles JS, Sims JE. Identification and characterization of two members of a novel class of the interleukin-1 receptor (IL-1R) family. Delineation Of a new class of IL-1R-related proteins based on signaling. J Biol Chem 2000; 275: 41528.
96. Khan JA, Brint EK, O'Neill LA, Tong L. Crystal structure of the Toll/interleukin-1 receptor domain of human IL-1RAPL. J Biol Chem 2004; 279: 31664-31670. (Pubitemid 39037837)
97. Thomas G, Lin D, Nuriya M, Huganir R. Rapid and bi-directional regulation of AMPA receptor phosphorylation and trafficking by JNK. EMBO J 2008; 27: 361-372. (Pubitemid 351161658)
98. Pavlowsky A, Zanchi A, Pallotto M, Giustetto M, Chelly J, Sala C et al. Neuronal JNK pathway activation by IL-1 is mediated through IL1RAPL1, a protein required for development of cognitive functions. Commun Integr Biol 2010; 3: 245-247.
99. Rothwell NJ, Luheshi GN. Interleukin 1 in the brain: biology, pathology and therapeutic target. Trends Neurosci 2000; 23: 618-625. (Pubitemid 32007888)
100. Ross FM, Allan SM, Rothwell NJ, Verkhratsky A. A dual role for interleukin-1 in LTP in mouse hippocampal slices. J Neuroimmunol 2003; 144: 61-67. (Pubitemid 37329930)
101. Avital A, Goshen I, Kamsler A, Segal M, Iverfeldt K, Richter-Levin G et al. Impaired interleukin-1 signaling is associated with deficits in hippocampal memory processes and neural plasticity. Hippocampus 2003; 13: 826-834. (Pubitemid 37407969)
102. Goshen I, Kreisel T, Ounallah-Saad H, Renbaum P, Zalzstein Y, Ben-Hur T et al. A dual role for interleukin-1 in hippocampaldependent memory processes. Psychoneuroendocrinology 2007; 32: 1106-1115. (Pubitemid 350086829)
103. Sudhof TC. Neuroligins and neurexins link synaptic function to cognitive disease. Nature 2008; 455: 903-911.
104. Chubykin AA, Atasoy D, Etherton MR, Brose N, Kavalali ET, Gibson JR et al. Activity-dependent validation of excitatory versus inhibitory synapses by neuroligin-1 versus neuroligin-2. Neuron 2007; 54: 919-931. (Pubitemid 46907504)
105. Etherton M, Foldy C, Sharma M, Tabuchi K, Liu X, Shamloo M et al. Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function. P Natl Acad Sci USA 2011; 108: 13764-13769.
106. Costa RM, Federov NB, Kogan JH, Murphy GG, Stern J, Ohno M et al. Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1. Nature 2002; 415: 526-530. (Pubitemid 34130607)
107. Li W, Cui Y, Kushner SA, Brown RA, Jentsch JD, Frankland PW et al. The HMG-CoA reductase inhibitor lovastatin reverses the learning and attention deficits in a mouse model of neurofibromatosis type 1. Curr Biol 2005; 15: 1961-1967. (Pubitemid 41566145)
108. Shilyansky C, Lee YS, Silva AJ. Molecular and cellular mechanisms of learning disabilities: a focus on NF1. Annu rev neurosci 2010; 33: 221-243.
109. Bowerman M, Beauvais A, Anderson CL, Kothary R. Rho-kinase inactivation prolongs survival of an intermediate SMA mouse model. Hum Mol Genet 2010; 19: 1468-1478.
110. Barman SA, Zhu S, White RE. RhoA/Rho-kinase signaling: a therapeutic target in pulmonary hypertension. Vasc Health Risk Manag 2009; 5: 663-671.
111. Calo LA, Pessina AC. RhoA/Rho-kinase pathway: much more than just a modulation of vascular tone. Evidence from studies in humans. J Hypertens 2007; 25: 259-264. (Pubitemid 46071919)
112. Dong M, Yan BP, Liao JK, Lam YY, Yip GW, Yu CM. Rho-kinase inhibition: a novel therapeutic target for the treatment of cardiovascular diseases. Drug Discov Today 2010; 15: 622-629.
113. Daouti S, Wang H, Li WH, Higgins B, Kolinsky K, Packman K et al. Characterization of a novel mitogen-activated protein kinase kinase 1/2 inhibitor with a unique mechanism of action for cancer therapy. Cancer Res 2009; 69: 1924-1932.
114. Messersmith WA, Hidalgo M, Carducci M, Eckhardt SG. Novel targets in solid tumors: MEK inhibitors. Clin Adv Hematol Oncol 2006; 4: 831-836. (Pubitemid 44883551)
115. Diana G, Valentini G, Travaglione S, Falzano L, Pieri M, Zona C et al. Enhancement of learning and memory after activation of cerebral Rho GTPases. P Natl Acad Sci USA 2007; 104: 636-641. (Pubitemid 46123077)