A neuronal function of the tumor suppressor protein merlin

Acta Neuropathologica Communications

Volumn 2, Issue 1, 2014, Pages

  Schulz, Alexander ^a,b   Zoch, Ansgar ^a   Morrison, Helen ^a  

^a FRITZ LIPMANN INSTITUTE   (Germany)

^b JENA UNIVERSITY HOSPITAL   (Germany)

Author keywords

Axon Schwann cell interaction; Intelligence; Merlin isoforms; Neurofibromatosis type 2; Peripheral neuropathy; Tumor development

Indexed keywords

ISOPROTEIN; MERLIN;

GENETICS; HUMAN; METABOLISM; MUTATION; NERVE CELL; NERVE FIBER; NEUROFIBROMATOSIS TYPE 2; POLYNEUROPATHY; SCHWANN CELL;

AXONS; HUMANS; MUTATION; NEUROFIBROMATOSIS 2; NEUROFIBROMIN 2; NEURONS; POLYNEUROPATHIES; PROTEIN ISOFORMS; SCHWANN CELLS;

EID: 84921751313     PISSN: None     EISSN: 20515960     Source Type: Journal    
DOI: 10.1186/s40478-014-0082-1     Document Type: Review

References (102)

1. Baser ME, R Evans DG, Gutmann DH: Neurofibromatosis 2. Curr Opin Neurol 2003, 16: 27-33. doi:10.1097/01.wco.0000053583.70044.ab 10.1097/00019052-200302000-00004
2. Evans DG, Kalamarides M, Hunter-Schaedle K, Blakeley J, Allen J, Babovic-Vuskanovic D, Belzberg A, Bollag G, Chen R, DiTomaso E, Golfinos J, Harris G, Jacob A, Kalpana G, Karajannis M, Korf B, Kurzrock R, Law M, McClatchey A, Packer R, Roehm P, Rubenstein A, Slattery W 3rd, Tonsgard JH, Welling DB, Widemann B, Yohay K, Giovannini M: Consensus recommendations to accelerate clinical trials for neurofibromatosis type 2. Clin Cancer Res 2009, 15: 5032-5039. doi:10.1158/1078-0432.CCR-08-3011 10.1158/1078-0432.CCR-08-3011
3. Roosli C, Linthicum FH Jr, Cureoglu S, Merchant SN: What is the site of origin of cochleovestibular schwannomas? Audiol Neurootol 2012, 17: 121-125. doi:10.1159/000331394 10.1159/000331394
4. Lee JH, Sundaram V, Stein DJ, Kinney SE, Stacey DW, Golubic M: Reduced expression of schwannomin/merlin in human sporadic meningiomas. Neurosurgery 1997, 40: 578-587.
5. Asthagiri AR, Parry DM, Butman JA, Kim HJ, Tsilou ET, Zhuang Z, Lonser RR: Neurofibromatosis type 2. Lancet 2009, 373: 1974-1986. doi:10.1016/S0140-6736(09)60259-2 10.1016/S0140-6736(09)60259-2
6. Gutmann DH, Wright DE, Geist RT, Snider WD: Expression of the neurofibromatosis 2 (NF2) gene isoforms during rat embryonic development. Hum Mol Genet 1995, 4: 471-478. 10.1093/hmg/4.3.471
7. McClatchey AI, Saotome I, Ramesh V, Gusella JF, Jacks T: The Nf2 tumor suppressor gene product is essential for extraembryonic development immediately prior to gastrulation. Genes Dev 1997, 11: 1253-1265. 10.1101/gad.11.10.1253
8. McLaughlin ME, Kruger GM, Slocum KL, Crowley D, Michaud NA, Huang J, Magendantz M, Jacks T: The Nf2 tumor suppressor regulates cell-cell adhesion during tissue fusion. Proc Natl Acad Sci U S A 2007, 104: 3261-3266. doi:10.1073/pnas.0700044104 10.1073/pnas.0700044104
9. Hanemann CO, Diebold R, Kaufmann D: Role of NF2 haploinsufficiency in NF2-associated polyneuropathy. Brain Pathol 2007, 17: 371-376. doi:10.1111/j.1750-3639.2007.00086.x 10.1111/j.1750-3639.2007.00086.x
10. Ramesh V: Merlin and the ERM proteins in Schwann cells, neurons and growth cones. Nat Rev Neurosci 2004, 5: 462-470. doi:10.1038/nrn1407 10.1038/nrn1407
11. Rouleau GA, Merel P, Lutchman M, Sanson M, Zucman J, Marineau C, Hoang-Xuan K, Demczuk S, Desmaze C, Plougastel B, Pulst SM, Lenoir G, Bijlsma E, Fashold R, Dumanski J, de Jong P, Parry D, Eldrige R, Aurias A, Delattre O, Thomas G: Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2. Nature 1993, 363: 515-521. doi:10.1038/363515a0 10.1038/363515a0
12. Trofatter JA, MacCollin MM, Rutter JL, Murrell JR, Duyao MP, Parry DM, Eldridge R, Kley N, Menon AG, Pulaski K, Haase VH, Ambrose CM, Munroe D, Bove C, Haines JL, Martuza RL, MacDonald ME, Seizinger BR, Short MP, Buckler AJ, James F, Gusella JF: A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell 1993, 72: 791-800. 10.1016/0092-8674(93)90406-G
13. McClatchey AI, Fehon RG: Merlin and the ERM proteins-regulators of receptor distribution and signaling at the cell cortex. Trends Cell Biol 2009, 19: 198-206. doi:10.1016/j.tcb.2009.02.006 10.1016/j.tcb.2009.02.006
14. Morrison H, Sherman LS, Legg J, Banine F, Isacke C, Haipek CA, Gutmann DH, Ponta H, Herrlich P: The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44. Genes Dev 2001, 15: 968-980. doi:10.1101/gad.189601 10.1101/gad.189601
15. Morrison H, Sperka T, Manent J, Giovannini M, Ponta H, Herrlich P: Merlin/neurofibromatosis type 2 suppresses growth by inhibiting the activation of Ras and Rac. Cancer Res 2007, 67: 520-527. doi:10.1158/0008-5472.CAN-06-1608 10.1158/0008-5472.CAN-06-1608
16. Li W, Cooper J, Karajannis MA, Giancotti FG: Merlin: a tumour suppressor with functions at the cell cortex and in the nucleus. EMBO Rep 2012, 13: 204-215. doi:10.1038/embor.2012.11 10.1038/embor.2012.11
17. Muranen T, Gronholm M, Renkema GH, Carpen O: Cell cycle-dependent nucleocytoplasmic shuttling of the neurofibromatosis 2 tumour suppressor merlin. Oncogene 2005, 24: 1150-1158. doi:10.1038/sj.onc.1208283 10.1038/sj.onc.1208283
18. Li W, You L, Cooper J, Schiavon G, Pepe-Caprio A, Zhou L, Ishii R, Giovannini M, Hanemann CO, Long SB, Erdjument-Bromage H, Zhou P, Tempst P, Giancotti FG: Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus. Cell 2010, 140: 477-490. doi:10.1016/j.cell.2010.01.029 10.1016/j.cell.2010.01.029
19. Mani T, Hennigan RF, Foster LA, Conrady DG, Herr AB, Ip W: FERM domain phosphoinositide binding targets merlin to the membrane and is essential for its growth-suppressive function. Mol Cell Biol 2011, 31: 1983-1996. doi:10.1128/MCB.00609-10 10.1128/MCB.00609-10
20. Scoles DR, Huynh DP, Chen MS, Burke SP, Gutmann DH, Pulst SM: The neurofibromatosis 2 tumor suppressor protein interacts with hepatocyte growth factor-regulated tyrosine kinase substrate. Hum Mol Genet 2000, 9: 1567-1574. 10.1093/hmg/9.11.1567
21. Muranen T, Gronholm M, Lampin A, Lallemand D, Zhao F, Giovannini M, Carpen O: The tumor suppressor merlin interacts with microtubules and modulates Schwann cell microtubule cytoskeleton. Hum Mol Genet 2007, 16: 1742-1751. doi:10.1093/hmg/ddm122 10.1093/hmg/ddm122
22. Scoles DR: The merlin interacting proteins reveal multiple targets for NF2 therapy. Biochim Biophys Acta 2008, 1785: 32-54. doi:10.1016/j.bbcan.2007.10.001
23. Yin F, Yu J, Zheng Y, Chen Q, Zhang N, Pan D: Spatial organization of Hippo signaling at the plasma membrane mediated by the tumor suppressor Merlin/NF2. Cell 2013, 154: 1342-1355. doi:10.1016/j.cell.2013.08.025 10.1016/j.cell.2013.08.025
24. Hall A: G proteins and small GTPases: distant relatives keep in touch. Science 1998, 280: 2074-2075. 10.1126/science.280.5372.2074
25. Luo L: Rho GTPases in neuronal morphogenesis. Nat Rev Neurosci 2000, 1: 173-180. doi:10.1038/35044547 10.1038/35044547
26. Schulz A, Geissler KJ, Kumar S, Leichsenring G, Morrison H, Baader SL: Merlin inhibits neurite outgrowth in the CNS. J Neurosci 2010, 30: 10177-10186. doi:10.1523/JNEUROSCI.0840-10.2010 10.1523/JNEUROSCI.0840-10.2010
27. Flaiz C, Kaempchen K, Matthies C, Hanemann CO: Actin-rich protrusions and nonlocalized GTPase activation in Merlin-deficient schwannomas. J Neuropathol Exp Neurol 2007, 66: 608-616. doi:10.1097/nen.0b013e318093e555 10.1097/nen.0b013e318093e555
28. Nadif Kasri N, Van Aelst L: Rho-linked genes and neurological disorders. Pflugers Arch 2008, 455: 787-797. doi:10.1007/s00424-007-0385-1 10.1007/s00424-007-0385-1
29. Golovnina K, Blinov A, Akhmametyeva EM, Omelyanchuk LV, Chang LS: Evolution and origin of merlin, the product of the Neurofibromatosis type 2 (NF2) tumor-suppressor gene. BMC Evol Biol 2005, 5: 69. doi:10.1186/1471-2148-5-69 10.1186/1471-2148-5-69
30. Scoles DR, Huynh DP, Morcos PA, Coulsell ER, Robinson NG, Tamanoi F, Pulst SM: Neurofibromatosis 2 tumour suppressor schwannomin interacts with betaII-spectrin. Nat Genet 1998, 18: 354-359. doi:10.1038/ng0498-354 10.1038/ng0498-354
31. Meng JJ, Lowrie DJ, Sun H, Dorsey E, Pelton PD, Bashour AM, Groden J, Ratner N, Ip W: Interaction between two isoforms of the NF2 tumor suppressor protein, merlin, and between merlin and ezrin, suggests modulation of ERM proteins by merlin. J Neurosci Res 2000, 62: 491-502. 10.1002/1097-4547(20001115)62:4<491::AID-JNR3>3.0.CO;2-D
32. Jannatipour M, Dion P, Khan S, Jindal H, Fan X, Laganiere J, Chishti AH, Rouleau GA: Schwannomin isoform-1 interacts with syntenin via PDZ domains. J Biol Chem 2001, 276: 33093-33100. doi:10.1074/jbc.M105792200 10.1074/jbc.M105792200
33. Lallemand D, Manent J, Couvelard A, Watilliaux A, Siena M, Chareyre F, Lampin A, Niwa-Kawakita M, Kalamarides M, Giovannini M: Merlin regulates transmembrane receptor accumulation and signaling at the plasma membrane in primary mouse Schwann cells and in human schwannomas. Oncogene 2009, 28: 854-865. doi:10.1038/onc.2008.427 10.1038/onc.2008.427
34. Jacoby LB, MacCollin M, Barone R, Ramesh V, Gusella JF: Frequency and distribution of NF2 mutations in schwannomas. Genes Chromosomes Cancer 1996, 17: 45-55. doi:10.1002/(SICI)1098-2264(199609)17:1<45::AID-GCC7>3.0.CO;2-2 10.1002/(SICI)1098-2264(199609)17:1<45::AID-GCC7>3.0.CO;2-2
35. Baser ME, Kuramoto L, Woods R, Joe H, Friedman JM, Wallace AJ, Ramsden RT, Olschwang S, Bijlsma E, Kalamarides M, Papi L, Kato R, Carroll J, Lazaro C, Joncourt F, Parry DM, Rouleau GA, Evans DG: The location of constitutional neurofibromatosis 2 (NF2) splice site mutations is associated with the severity of NF2. J Med Genet 2005, 42: 540-546. doi:10.1136/jmg.2004.029504 10.1136/jmg.2004.029504
36. Sherman L, Xu HM, Geist RT, Saporito-Irwin S, Howells N, Ponta H, Herrlich P, Gutmann DH: Interdomain binding mediates tumor growth suppression by the NF2 gene product. Oncogene 1997, 15: 2505-2509. doi:10.1038/sj.onc.1201418 10.1038/sj.onc.1201418
37. Gutmann DH, Sherman L, Seftor L, Haipek C, Hoang Lu K, Hendrix M: Increased expression of the NF2 tumor suppressor gene product, merlin, impairs cell motility, adhesionand spreading. Hum Mol Genet 1999, 8: 267-275. doi:ddc028 10.1093/hmg/8.2.267
38. James MF, Han S, Polizzano C, Plotkin SR, Manning BD, Stemmer-Rachamimov AO, Gusella JF, Ramesh V: NF2/merlin is a novel negative regulator of mTOR complex 1, and activation of mTORC1 is associated with meningioma and schwannoma growth. Mol Cell Biol 2009, 29: 4250-4261. doi:10.1128/MCB.01581-08 10.1128/MCB.01581-08
39. Laulajainen M, Melikova M, Muranen T, Carpen O, Gronholm M: Distinct overlapping sequences at the carboxy-terminus of merlin regulate its tumour suppressor and morphogenic activity. J Cell Mol Med 2012, 16: 2161-2175. doi:10.1111/j.1582-4934.2012.01525.x 10.1111/j.1582-4934.2012.01525.x
40. Zhan Y, Modi N, Stewart AM, Hieronimus RI, Liu J, Gutmann DH, Chadee DN: Regulation of mixed lineage kinase 3 is required for Neurofibromatosis-2-mediated growth suppression in human cancer. Oncogene 2011, 30: 781-789. doi:10.1038/onc.2010.453 10.1038/onc.2010.453
41. Gavilan HS, Kulikauskas RM, Gutmann DH, Fehon RG: In Vivo Functional Analysis of the Human NF2 Tumor Suppressor Gene in Drosophila. PLoS One 2014, 9: e90853. doi:10.1371/journal.pone.0090853 10.1371/journal.pone.0090853
42. Bianchi AB, Hara T, Ramesh V, Gao J, Klein-Szanto AJ, Morin F, Menon AG, Trofatter JA, Gusella JF, Seizinger BR, Kley N: Mutations in transcript isoforms of the neurofibromatosis 2 gene in multiple human tumour types. Nat Genet 1994, 6: 185-192. doi:10.1038/ng0294-185 10.1038/ng0294-185
43. Schmucker B, Tang Y, Kressel M: Novel alternatively spliced isoforms of the neurofibromatosis type 2 tumor suppressor are targeted to the nucleus and cytoplasmic granules. Hum Mol Genet 1999, 8: 1561-1570. 10.1093/hmg/8.8.1561
44. Huynh DP, Tran TM, Nechiporuk T, Pulst SM: Expression of neurofibromatosis 2 transcript and gene product during mouse fetal development. Cell Growth Differ 1996, 7: 1551-1561.
45. Schulz A, Baader SL, Niwa-Kawakita M, Jung MJ, Bauer R, Garcia C, Zoch A, Schacke S, Hagel C, Mautner VF, Hanemann CO, Dun XP, Parkinson DB, Weis J, Schroder JM, Gutmann DH, Giovannini M, Morrison H: Merlin isoform 2 in neurofibromatosis type 2-associated polyneuropathy. Nat Neurosci 2013, 16: 426-433. doi:10.1038/nn.3348 10.1038/nn.3348
46. den Bakker MA, Vissers KJ, Molijn AC, Kros JM, Zwarthoff EC, van der Kwast TH: Expression of the neurofibromatosis type 2 gene in human tissues. J Histochem Cytochem 1999, 47: 1471-1480. 10.1177/002215549904701113
47. Claudio JO, Lutchman M, Rouleau GA: Widespread but cell type-specific expression of the mouse neurofibromatosis type 2 gene. Neuroreport 1995, 6: 1942-1946. 10.1097/00001756-199510020-00028
48. Wang Q, Zhou D, Yan B, Lin X, Zhang SF: [Expression of Merlin in cortex of temporal lobe and in hippocampal CA1 region of the Kindling Model of Epilepsy induced by corciaria lactone in rats]. Sichuan Da Xue Xue Bao Yi Xue Ban 2006, 37: 115-117.
49. Chen Y, Yu P, Lu D, Tagle DA, Cai T: A novel isoform of beta-spectrin II localizes to cerebellar Purkinje-cell bodies and interacts with neurofibromatosis type 2 gene product schwannomin. J Mol Neurosci 2001, 17: 59-70. doi:10.1385/JMN:17:1:59 10.1385/JMN:17:1:59
50. Lavado A, He Y, Pare J, Neale G, Olson EN, Giovannini M, Cao X: Tumor suppressor Nf2 limits expansion of the neural progenitor pool by inhibiting Yap/Taz transcriptional coactivators. Development 2013, 140: 3323-3334. doi:10.1242/dev.096537 10.1242/dev.096537
51. Gronholm M, Teesalu T, Tyynela J, Piltti K, Bohling T, Wartiovaara K, Vaheri A, Carpen O: Characterization of the NF2 protein merlin and the ERM protein ezrin in human, rat, and mouse central nervous system. Mol Cell Neurosci 2005, 28: 683-693. doi:10.1016/j.mcn.2004.11.014 10.1016/j.mcn.2004.11.014
52. Seo PS, Quinn BJ, Khan AA, Zeng L, Takoudis CG, Hanada T, Bolis A, Bolino A, Chishti AH: Identification of erythrocyte p55/MPP1 as a binding partner of NF2 tumor suppressor protein/Merlin. Exp Biol Med (Maywood) 2009, 234: 255-262. doi:10.3181/0809-RM-275 10.3181/0809-RM-275
53. Stemmer-Rachamimov AO, Gonzalez-Agosti C, Xu L, Burwick JA, Beauchamp R, Pinney D, Louis DN, Ramesh V: Expression of NF2-encoded merlin and related ERM family proteins in the human central nervous system. J Neuropathol Exp Neurol 1997, 56: 735-742. 10.1097/00005072-199706000-00011
54. England JD, Asbury AK: Peripheral neuropathy. Lancet 2004, 363: 2151-2161. doi:10.1016/S0140-6736(04)16508-2 10.1016/S0140-6736(04)16508-2
55. Evans DG, Huson SM, Donnai D, Neary W, Blair V, Newton V, Harris R: A clinical study of type 2 neurofibromatosis. Q J Med 1992, 84: 603-618.
56. Sperfeld AD, Hein C, Schroder JM, Ludolph AC, Hanemann CO: Occurrence and characterization of peripheral nerve involvement in neurofibromatosis type 2. Brain 2002, 125: 996-1004. 10.1093/brain/awf115
57. MacCollin M (1999) Clinical aspects. In: Friedman JM, Gutmann DH, MacCollin M, Riccardi VM (eds). Johns Hopkins University Press, Baltimore, pp 299-326
58. Kimura J: Electrodiagnosis in Diseases of Nerve and Muscle: Principles and Practice. Oxford University Press, USA, City; 2001.
59. Grazzi L, Chiapparini L, Parati EA, Giombini S, D'Amico D, Leone M, Bussone G: Type II neurofibromatosis presenting as quadriceps atrophy. Ital J Neurol Sci 1998, 19: 94-96. 10.1007/BF02427564
60. Hagel C, Lindenau M, Lamszus K, Kluwe L, Stavrou D, Mautner VF: Polyneuropathy in neurofibromatosis 2: clinical findings, molecular genetics and neuropathological alterations in sural nerve biopsy specimens. Acta Neuropathol 2002, 104: 179-187. doi:10.1007/s00401-002-0535-7 10.1007/s00401-002-0535-7
61. Baumer P, Mautner VF, Baumer T, Schuhmann MU, Tatagiba M, Heiland S, Kaestel T, Bendszus M, Pham M: Accumulation of non-compressive fascicular lesions underlies NF2 polyneuropathy. J Neurol 2013, 260: 38-46. doi:10.1007/s00415-012-6581-8 10.1007/s00415-012-6581-8
62. Iwata A, Kunimoto M, Inoue K: Schwann cell proliferation as the cause of peripheral neuropathy in neurofibromatosis-2. J Neurol Sci 1998, 156: 201-204. 10.1016/S0022-510X(98)00032-X
63. Iseki C, Takahashi Y, Wada M, Kawanami T, Kurita K, Kato T: A case of neurofibromatosis type 2 (NF2) presenting with late-onset axonal polyneuropathy. Rinsho Shinkeigaku 2009, 49: 419-423. 10.5692/clinicalneurol.49.419
64. Kuo HC, Chen SR, Jung SM, Wu Chou YH, Huang CC, Chuang WL, Wei KC, Ro LS (2010) Neurofibromatosis 2 with peripheral neuropathies: Electrophysiological, pathological and genetic studies of a Taiwanese family. Neuropathology doi:10.1111/j.1440-1789.2009.01099.x
65. Bosch EP, Murphy MJ, Cancilla PA: Peripheral neurofibromatosis and peroneal muscular atrophy. Neurology 1981, 31: 1408-1414. 10.1212/WNL.31.11.1408
66. Overweg-Plandsoen WC, Brouwer-Mladin R, Merel P, de Vries L, Bijlsma EK: Neurofibromatosis type 2 in an adolescent boy with polyneuropathy and a mutation in the NF2 gene. J Neurol 1996, 243: 724-726. 10.1007/BF00873979
67. Perrot R, Berges R, Bocquet A, Eyer J: Review of the multiple aspects of neurofilament functions, and their possible contribution to neurodegeneration. Mol Neurobiol 2008, 38: 27-65. doi:10.1007/s12035-008-8033-0 10.1007/s12035-008-8033-0
68. Maeda M, Matsui T, Imamura M, Tsukita S: Expression level, subcellular distribution and rho-GDI binding affinity of merlin in comparison with Ezrin/Radixin/Moesin proteins. Oncogene 1999, 18: 4788-4797. doi:10.1038/sj.onc.1202871 10.1038/sj.onc.1202871
69. Bretscher A, Edwards K, Fehon RG: ERM proteins and merlin: integrators at the cell cortex. Nat Rev Mol Cell Biol 2002, 3: 586-599. doi:10.1038/nrm882 10.1038/nrm882
70. Corfas G, Velardez MO, Ko CP, Ratner N, Peles E: Mechanisms and roles of axon-Schwann cell interactions. J Neurosci 2004, 24: 9250-9260. doi:10.1523/JNEUROSCI.3649-04.2004 10.1523/JNEUROSCI.3649-04.2004
71. Hanemann CO: Magic but treatable? Tumours due to loss of merlin. Brain 2008, 131: 606-615. doi:10.1093/brain/awm249 10.1093/brain/awm249
72. Denisenko N, Cifuentes-Diaz C, Irinopoulou T, Carnaud M, Benoit E, Niwa-Kawakita M, Chareyre F, Giovannini M, Girault JA, Goutebroze L: Tumor suppressor schwannomin/merlin is critical for the organization of Schwann cell contacts in peripheral nerves. J Neurosci 2008, 28: 10472-10481. doi:10.1523/JNEUROSCI.2537-08.2008 10.1523/JNEUROSCI.2537-08.2008
73. Thaxton C, Bott M, Walker B, Sparrow NA, Lambert S, Fernandez-Valle C: Schwannomin/merlin promotes Schwann cell elongation and influences myelin segment length. Mol Cell Neurosci 2011, 47: 1-9. doi:10.1016/j.mcn.2010.12.006 10.1016/j.mcn.2010.12.006
74. Jessen KR, Mirsky R: The origin and development of glial cells in peripheral nerves. Nat Rev Neurosci 2005, 6: 671-682. doi:10.1038/nrn1746 10.1038/nrn1746
75. Michailov GV, Sereda MW, Brinkmann BG, Fischer TM, Haug B, Birchmeier C, Role L, Lai C, Schwab MH, Nave KA: Axonal neuregulin-1 regulates myelin sheath thickness. Science 2004, 304: 700-703. doi:10.1126/science.1095862 10.1126/science.1095862
76. Taveggia C, Zanazzi G, Petrylak A, Yano H, Rosenbluth J, Einheber S, Xu X, Esper RM, Loeb JA, Shrager P, Chao MV, Falls DL, Role L, Salzer JL: Neuregulin-1 type III determines the ensheathment fate of axons. Neuron 2005, 47: 681-694. doi:10.1016/j.neuron.2005.08.017 10.1016/j.neuron.2005.08.017
77. Scherer SS, Salzer JL: Axon-Schwann cell interactions during peripheral nerve degeneration and regeneration. Glial Cell Dev: Basic Princ Clinl Relevance 2001, 2: 165-196.
78. Gijtenbeek JM, Gabreels-Festen AA, Lammens M, Zwarts MJ, van Engelen BG: Mononeuropathy multiplex as the initial manifestation of neurofibromatosis type 2. Neurology 2001, 56: 1766-1768. 10.1212/WNL.56.12.1766
79. Fricker FR, Bennett DL: The role of neuregulin-1 in the response to nerve injury. Future Neurol 2011, 6: 809-822. 10.2217/fnl.11.45
80. Denisenko-Nehrbass N, Goutebroze L, Galvez T, Bonnon C, Stankoff B, Ezan P, Giovannini M, Faivre-Sarrailh C, Girault JA: Association of Caspr/paranodin with tumour suppressor schwannomin/merlin and beta1 integrin in the central nervous system. J Neurochem 2003, 84: 209-221. 10.1046/j.1471-4159.2003.01503.x
81. Zhang C, Susuki K, Zollinger DR, Dupree JL, Rasband MN: Membrane domain organization of myelinated axons requires betaII spectrin. J Cell Biol 2013, 203: 437-443. doi:10.1083/jcb.201308116 10.1083/jcb.201308116
82. Salzer JL, Brophy PJ, Peles E: Molecular domains of myelinated axons in the peripheral nervous system. Glia 2008, 56: 1532-1540. doi:10.1002/glia.20750 10.1002/glia.20750
83. Gronholm M, Vossebein L, Carlson CR, Kuja-Panula J, Teesalu T, Alfthan K, Vaheri A, Rauvala H, Herberg FW, Tasken K, Carpen O: Merlin links to the cAMP neuronal signaling pathway by anchoring the RIbeta subunit of protein kinase A. J Biol Chem 2003, 278: 41167-41172. doi:10.1074/jbc.M306149200 10.1074/jbc.M306149200
84. Yamauchi J, Miyamoto Y, Kusakawa S, Torii T, Mizutani R, Sanbe A, Nakajima H, Kiyokawa N, Tanoue A: Neurofibromatosis 2 tumor suppressor, the gene induced by valproic acid, mediates neurite outgrowth through interaction with paxillin. Exp Cell Res 2008, 314: 2279-2288. doi:10.1016/j.yexcr.2008.03.019 10.1016/j.yexcr.2008.03.019
85. Schulz A, Kyselyova A, Baader SL, Jung MJ, Zoch A, Mautner VF, Hagel C, Morrison H (2014) Neuronal merlin influences ERBB2 receptor expression on Schwann cells through neuregulin 1 type III signalling. Brain doi:10.1093/brain/awt327
86. Citri A, Skaria KB, Yarden Y: The deaf and the dumb: the biology of ErbB-2 and ErbB-3. Exp Cell Res 2003, 284: 54-65. 10.1016/S0014-4827(02)00101-5
87. Zanazzi G, Einheber S, Westreich R, Hannocks MJ, Bedell-Hogan D, Marchionni MA, Salzer JL: Glial growth factor/neuregulin inhibits Schwann cell myelination and induces demyelination. J Cell Biol 2001, 152: 1289-1299. 10.1083/jcb.152.6.1289
88. Massa R, Palumbo C, Cavallaro T, Panico MB, Bei R, Terracciano C, Rizzuto N, Bernardi G, Modesti A: Overexpression of ErbB2 and ErbB3 receptors in Schwann cells of patients with Charcot-Marie-tooth disease type 1A. Muscle Nerve 2006, 33: 342-349. doi:10.1002/mus.20460 10.1002/mus.20460
89. Sherman LS, Rizvi TA, Karyala S, Ratner N: CD44 enhances neuregulin signaling by Schwann cells. J Cell Biol 2000, 150: 1071-1084. 10.1083/jcb.150.5.1071
90. Thaxton C, Lopera J, Bott M, Fernandez-Valle C: Neuregulin and laminin stimulate phosphorylation of the NF2 tumor suppressor in Schwann cells by distinct protein kinase A and p21-activated kinase-dependent pathways. Oncogene 2008, 27: 2705-2715. doi:10.1038/sj.onc.1210923 10.1038/sj.onc.1210923
91. Clark JJ, Provenzano M, Diggelmann HR, Xu N, Hansen SS, Hansen MR: The ErbB inhibitors trastuzumab and erlotinib inhibit growth of vestibular schwannoma xenografts in nude mice: a preliminary study. Otol Neurotol 2008, 29: 846-853. Doi 10.1097/MAO.0b013e31817f7398 10.1097/MAO.0b013e31817f7398
92. Ammoun S, Cunliffe CH, Allen JC, Chiriboga L, Giancotti FG, Zagzag D, Hanemann CO, Karajannis MA: ErbB/HER receptor activation and preclinical efficacy of lapatinib in vestibular schwannoma. Neuro-Oncology 2010, 12: 834-843. doi:10.1093/neuonc/noq012 10.1093/neuonc/noq012
93. Parrinello S, Noon LA, Harrisingh MC, Wingfield Digby P, Rosenberg LH, Cremona CA, Echave P, Flanagan AM, Parada LF, Lloyd AC: NF1 loss disrupts Schwann cell-axonal interactions: a novel role for semaphorin 4F. Genes Dev 2008, 22: 3335-3348. doi:10.1101/gad.490608 10.1101/gad.490608
94. Joseph NM, Mosher JT, Buchstaller J, Snider P, McKeever PE, Lim M, Conway SJ, Parada LF, Zhu Y, Morrison SJ: The loss of Nf1 transiently promotes self-renewal but not tumorigenesis by neural crest stem cells. Cancer Cell 2008, 13: 129-140. doi:10.1016/j.ccr.2008.01.003 10.1016/j.ccr.2008.01.003
95. James MF, Manchanda N, Gonzalez-Agosti C, Hartwig JH, Ramesh V: The neurofibromatosis 2 protein product merlin selectively binds F-actin but not G-actin, and stabilizes the filaments through a lateral association. Biochem J 2001, 356: 377-386. 10.1042/0264-6021:3560377
96. Xu HM, Gutmann DH: Merlin differentially associates with the microtubule and actin cytoskeleton. J Neurosci Res 1998, 51: 403-415. 10.1002/(SICI)1097-4547(19980201)51:3<403::AID-JNR13>3.0.CO;2-7
97. Hadfield KD, Smith MJ, Urquhart JE, Wallace AJ, Bowers NL, King AT, Rutherford SA, Trump D, Newman WG, Evans DG: Rates of loss of heterozygosity and mitotic recombination in NF2 schwannomas, sporadic vestibular schwannomas and schwannomatosis schwannomas. Oncogene 2010, 29: 6216-6221. doi:10.1038/onc.2010.363 10.1038/onc.2010.363
98. Stemmer-Rachamimov AO, Ino Y, Lim ZY, Jacoby LB, MacCollin M, Gusella JF, Ramesh V, Louis DN: Loss of the NF2 gene and merlin occur by the tumorlet stage of schwannoma development in neurofibromatosis 2. J Neuropathol Exp Neurol 1998, 57: 1164-1167. 10.1097/00005072-199812000-00008
99. Huang YY, Kandel ER, Varshavsky L, Brandon EP, Qi M, Idzerda RL, McKnight GS, Bourtchouladze R: A genetic test of the effects of mutations in PKA on mossy fiber LTP and its relation to spatial and contextual learning. Cell 1995, 83: 1211-1222. 10.1016/0092-8674(95)90146-9
100. Wassink TH, Brzustowicz LM, Bartlett CW, Szatmari P: The search for autism disease genes. Ment Retard Dev Disabil Res Rev 2004, 10: 272-283. doi:10.1002/mrdd.20041 10.1002/mrdd.20041
101. Penzes P, Cahill ME, Jones KA, VanLeeuwen JE, Woolfrey KM: Dendritic spine pathology in neuropsychiatric disorders. Nat Neurosci 2011, 14: 285-293. doi:10.1038/nn.2741 10.1038/nn.2741
102. Murakoshi H, Wang H, Yasuda R: Local, persistent activation of Rho GTPases during plasticity of single dendritic spines. Nature 2011, 472: 100-104. doi:10.1038/nature09823 10.1038/nature09823