Neurofilament phosphorylation and their proline-directed kinases in health and disease

Journal of the Peripheral Nervous System

Volumn 17, Issue 4, 2012, Pages 365-376

  Holmgren, Anne ^a,b   Bouhy, Delphine ^a,b   Timmerman, Vincent ^a,b  

^a UNIVERSITY OF ANTWERP   (Belgium)

^b UNIVERSITY OF ANTWERP   (Belgium)

Author keywords

kinase; neurodegenerative diseases; neurofilaments; phosphatase; phosphorylation

Indexed keywords

ALPHA INTERNEXIN; CYCLIN DEPENDENT KINASE 5; EPIDERMAL GROWTH FACTOR; LAMININ; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; MITOGEN ACTIVATED PROTEIN KINASE KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE KINASE 2; NEUROFILAMENT M PROTEIN; NEUROFILAMENT PROTEIN; PHOSPHOPROTEIN PHOSPHATASE 1; PROLINE DIRECTED PROTEIN KINASE; RAS PROTEIN;

APOPTOSIS; CARBOXY TERMINAL SEQUENCE; DEGENERATIVE DISEASE; HUMAN; IN VIVO STUDY; INTERMEDIATE FILAMENT; NERVE CELL DIFFERENTIATION; NERVE FIBER; NERVE FIBER TRANSPORT; NEUROFILAMENT; NONHUMAN; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN ASSEMBLY; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN TRANSPORT; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; DISEASE; HEALTH; HUMANS; INTERMEDIATE FILAMENTS; NERVE DEGENERATION; NEUROFILAMENT PROTEINS; NEURONS; PHOSPHORYLATION; PROLINE; PROTEIN KINASES;

EID: 84872833125     PISSN: 10859489     EISSN: 15298027     Source Type: Journal    
DOI: 10.1111/j.1529-8027.2012.00434.x     Document Type: Review

References (124)

1. Ackerley S, Grierson AJ, Brownlees J, Thornhill P, Anderton BH, Leigh PN, Shaw CE, Miller CC, (2000). Glutamate slows axonal transport of neurofilaments in transfected neurons. J Cell Biol 150: 165-176.
2. Ackerley S, Thornhill P, Grierson AJ, Brownlees J, Anderton BH, Leigh PN, Shaw CE, Miller CC, (2003). Neurofilament heavy chain side arm phosphorylation regulates axonal transport of neurofilaments. J Cell Biol 161: 489-495.
3. Ackerley S, Grierson AJ, Banner S, Perkinton MS, Brownlees J, Byers HL, Ward M, Thornhill P, Hussain K, Waby JS, Anderton BH, Cooper JD, Dingwall C, Leigh PN, Shaw CE, Miller CC, (2004). p38alpha stress-activated protein kinase phosphorylates neurofilaments and is associated with neurofilament pathology in amyotrophic lateral sclerosis. Mol Cell Neurosci 26: 354-364.
4. Alberts B, (1998). The cell as a collection of protein machines: preparing the next generation of molecular biologists. Cell 92: 291-294.
5. Al-Chalabi A, Andersen PM, Nilsson P, Chioza B, Andersson JL, Russ C, Shaw CE, Powell JF, Leigh PN, (1999). Deletions of the heavy neurofilament subunit tail in amyotrophic lateral sclerosis. Hum Mol Genet 8: 157-164.
6. Angelides KJ, Smith KE, Takeda M, (1989). Assembly and exchange of intermediate filament proteins of neurons: neurofilaments are dynamic structures. J Cell Biol 108: 1495-1506.
7. Bajaj NP, Miller CC, (1997). Phosphorylation of neurofilament heavy-chain side-arm fragments by cyclin-dependent kinase-5 and glycogen synthase kinase-3alpha in transfected cells. J Neurochem 69: 737-743.
8. Beaulieu JM, Robertson J, Julien JP, (1999). Interactions between peripherin and neurofilaments in cultured cells: disruption of peripherin assembly by the NF-M and NF-H subunits. Biochem Cell Biol 77: 41-45.
9. Black MM, Lee VM, (1988). Phosphorylation of neurofilament proteins in intact neurons: demonstration of phosphorylation in cell bodies and axons. J Neurosci 8: 3296-3305.
10. Bocquet A, Berges R, Frank R, Robert P, Peterson AC, Eyer J, (2009). Neurofilaments bind tubulin and modulate its polymerization. J Neurosci 29: 11043-11054.
11. Brettschneider J, Petzold A, Sussmuth SD, Ludolph AC, Tumani H, (2006a). Axonal damage markers in cerebrospinal fluid are increased in ALS. Neurology 66: 852-856.
12. Brettschneider J, Petzold A, Schottle D, Claus A, Riepe M, Tumani H, (2006b). The neurofilament heavy chain (NfH) in the cerebrospinal fluid diagnosis of Alzheimer's disease. Dement Geriatr Cogn Disord 21: 291-295.
13. Brown A, Wang L, Jung P, (2005). Stochastic simulation of neurofilament transport in axons: the «stop-and-go» hypothesis. Mol Biol Cell 16: 4243-4255.
14. Brownlees J, Ackerley S, Grierson AJ, Jacobson NJO, Shea K, Anderton BH, Leigh PN, Shaw CE, Miller CCJ, (2002). Charcot-Marie-Tooth disease neurofilament mutations disrupt neurofilament assembly and axonal transport. Hum Mol Genet 11: 2837-2844.
15. Cantuti-Castelvetri L, Zhu H, Givogri MI, Chidavainzi RL, Lopez-Rosas A, Bongarzone ER, (2012). Psychosine induces the dephosphorylation of neurofilaments by deregulation of PP1 and PP2A phosphatases. Neurobiol Dis 46: 325-335.
16. Carden MJ, Trojanowski JQ, Schlaepfer WW, Lee VM, (1987). Two-stage expression of neurofilament polypeptides during rat neurogenesis with early establishment of adult phosphorylation patterns. J Neurosci 7: 3489-3504.
17. Chan WK, Dickerson A, Ortiz D, Pimenta AF, Moran CM, Motil J, Snyder SJ, Malik K, Pant HC, Shea TB, (2004). Mitogen-activated protein kinase regulates neurofilament axonal transport. J Cell Sci 117: 4629-4642.
18. Chan WK, Yabe JT, Pimenta AF, Ortiz D, Shea TB, (2005). Neurofilaments can undergo axonal transport and cytoskeletal incorporation in a discontinuous manner. Cell Motil Cytoskeleton 62: 166-179.
19. Clark EA, Lee VM, (1991). Dynamics of mammalian high-molecular-weight neurofilament subunit phosphorylation in cultured rat sympathetic neurons. J Neurosci Res 30: 116-123.
20. Coleman M, (2011). Molecular signaling how do axons die? Adv Genet 73: 185-217.
21. Collard JF, Cote F, Julien JP, (1995). Defective axonal transport in a transgenic mouse model of amyotrophic lateral sclerosis. Nature 375: 61-64.
22. Cote F, Collard JF, Julien JP, (1993). Progressive neuronopathy in transgenic mice expressing the human neurofilament heavy gene: a mouse model of amyotrophic lateral sclerosis. Cell 73: 35-46.
23. Craciun G, Brown A, Friedman A, (2005). A dynamical system model of neurofilament transport in axons. J Theor Biol 237: 316-322.
24. Dashiell SM, Tanner SL, Pant HC, Quarles RH, (2002). Myelin-associated glycoprotein modulates expression and phosphorylation of neuronal cytoskeletal elements and their associated kinases. J Neurochem 81: 1263-1272.
25. Dequen F, Filali M, Larivière RC, Perrot R, Hisanaga S, Julien JP, (2010). Reversal of neuropathy phenotypes in conditional mouse model of Charcot-Marie-Tooth disease type 2E. Hum Mol Genet 19: 2616-2629.
26. Figlewicz DA, Krizus A, Martinoli MG, Meininger V, Dib M, Rouleau GA, Julien JP, (1994). Variants of the heavy neurofilament subunit are associated with the development of amyotrophic lateral sclerosis. Hum Mol Genet 3: 1757-1761.
27. Floyd CC, Grant P, Gallant PE, Pant HC, (1991). Principal neurofilament-associated protein kinase in squid axoplasm is related to casein kinase I. J Biol Chem 266: 4987-4994.
28. Friede RL, Samorajski T, (1970). Axon calibre related to neurofilaments and microtubules in sciatic nerve fibers of rats and mice. Anat Rec 167: 379-388.
29. Giasson BI, Mushynski WE, (1997). Study of proline-directed protein kinases involved in phosphorylation of the heavy neurofilament subunit. J Neurosci 17: 9466-9472.
30. Glicksman MA, Soppet D, Willard MB, (1987). Posttranslational modification of neurofilament polypeptides in rabbit retina. J Neurobiol 18: 167-196.
31. Goldstein ME, Sternberger NH, Sternberger LA, (1987). Phosphorylation protects neurofilaments against proteolysis. J Neuroimmunol 14: 149-160.
32. Grant P, Diggins M, Pant HC, (1999). Topographic regulation of cytoskeletal protein phosphorylation by multimeric complexes in the squid giant fiber system. J Neurobiol 40: 89-102.
33. Grant P, Sharma P, Pant HC, (2001). Cyclin-dependent protein kinase 5 (Cdk5) and the regulation of neurofilament metabolism. Eur J Biochem 268: 1534-1546.
34. Guan RJ, Khatra BS, Cohlberg JA, (1991). Phosphorylation of bovine neurofilament proteins by protein kinase FA (glycogen synthase kinase 3). J Biol Chem 266: 8262-8267.
35. Hallows JL, Chen K, DePinho RA, Vincent I, (2003). Decreased cyclin-dependent kinase 5 (cdk5) activity is accompanied by redistribution of cdk5 and cytoskeletal proteins and increased cytoskeletal protein phosphorylation in p35 null mice. J Neurosci 23: 10633-10644.
36. Hirokawa N, (1982). Cross-linker system between neurofilaments, microtubules, and membranous organelles in frog axons revealed by the quick-freeze, deep-etching method. J Cell Biol 94: 129-142.
37. Hirokawa N, Glicksman MA, Willard MB, (1984). Organization of mammalian neurofilament polypeptides within the neuronal cytoskeleton. J Cell Biol 98: 1523-1536.
38. Hisanaga S, Hirokawa N, (1989). The effects of dephosphorylation on the structure of the projections of neurofilament. J Neurosci 9: 959-966.
39. Hsieh ST, Kidd GJ, Crawford TO, Xu Z, Lin WM, Trapp BD, Cleveland DW, Griffin JW, (1994). Regional modulation of neurofilament organization by myelination in normal axons. J Neurosci 14: 6392-6401.
40. Jacomy H, Zhu Q, Couillard-Despres S, Beaulieu JM, Julien JP, (1999). Disruption of type IV intermediate filament network in mice lacking the neurofilament medium and heavy subunits. J Neurochem 73: 972-984.
41. Jordanova A, De Jonghe P, Boerkoel CF, Takashima H, De Vriendt E, Ceuterick C, Butler I, Mancias P, Papasozomenos SCH, Terespolski D, Potocki L, Brown CW, Shy M, Rita DA, Tournev I, Kremensky I, Lupski JR, Timmerman V, (2003). Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot-Marie-Tooth disease. Brain 126: 590-597.
42. Julien JP, Mushynski WE, (1982). Multiple phosphorylation sites in mammalian neurofilament polypeptides. J Biol Chem 257: 10467-10470.
43. Jung C, Shea TB, (1999). Regulation of neurofilament axonal transport by phosphorylation in optic axons in situ. Cell Motil Cytoskeleton 42: 230-240.
44. Jung C, Lee S, Ortiz D, Zhu Q, Julien JP, Shea TB, (2005). The high and middle molecular weight neurofilament subunits regulate the association of neurofilaments with kinesin: inhibition by phosphorylation of the high molecular weight subunit. Brain Res Mol Brain Res 141: 151-155.
45. Lee KY, Johnston RN, (1997). Neurofilaments are part of the high molecular weight complex containing neuronal cdc2-like kinase (nclk). Brain Res 773: 197-202.
46. Lee MK, Marszalek JR, Cleveland DW, (1994). A mutant neurofilament subunit causes massive, selective motor neuron death: implications for the pathogenesis of human motor neuron disease. Neuron 13: 975-988.
47. Lee S, Sunil N, Shea TB, (2011). C-terminal neurofilament phosphorylation fosters neurofilament-neurofilament associations that compete with axonal transport. Cytoskeleton (Hoboken) 68: 8-17.
48. Lewis SE, Nixon RA, (1988). Multiple phosphorylated variants of the high molecular mass subunit of neurofilaments in axons of retinal cell neurons: characterization and evidence for their differential association with stationary and moving neurofilaments. J Cell Biol 107: 2689-2701.
49. Li BS, Veeranna GJ, Grant P, Pant HC, (1999). Activation of mitogen-activated protein kinases (Erk1 and Erk2) cascade results in phosphorylation of NF-M tail domains in transfected NIH 3T3 cells. Eur J Biochem 262: 211-217.
50. Li BS, Zhang L, Gu J, Amin ND, Pant HC, (2000). Integrin alpha(1) beta(1)-mediated activation of cyclin-dependent kinase 5 activity is involved in neurite outgrowth and human neurofilament protein H Lys-Ser-Pro tail domain phosphorylation. J Neurosci 20: 6055-6062.
51. Li BS, Daniels MP, Pant HC, (2001). Integrins stimulate phosphorylation of neurofilament NF-M subunit KSP repeats through activation of extracellular regulated-kinases (Erk1/Erk2) in cultured motoneurons and transfected NIH 3T3 cells. J Neurochem 76: 703-710.
52. Liu Q, Xie F, Alvarado-Diaz A, Smith MA, Moreira PI, Zhu X, Perry G, (2011). Neurofilamentopathy in neurodegenerative diseases. Open Neurol J 5: 58-62.
53. Lobsiger CS, Garcia ML, Ward CM, Cleveland DW, (2005). Altered axonal architecture by removal of the heavily phosphorylated neurofilament tail domains strongly slows superoxide dismutase 1 mutant-mediated ALS. Proc Natl Acad Sci U S A 102: 10351-10356.
54. Marszalek JR, Williamson TL, Lee MK, Xu Z, Hoffman PN, Becher MW, Crawford TO, Cleveland DW, (1996). Neurofilament subunit NF-H modulates axonal diameter by selectively slowing neurofilament transport. J Cell Biol 135: 711-724.
55. Mersiyanova IV, Perepelov AV, Polyakov AV, Sitnikov VF, Dadali EL, Oparin RB, Petrin A, Evgrafov OV, (2000). A new variant of Charcot-Marie-Tooth disease type 2 (CMT2E) is probably the result of a mutation in the neurofilament light gene. Am J Hum Genet 67: 37-46.
56. Miyasaka H, Okabe S, Ishiguro K, Uchida T, Hirokawa N, (1993). Interaction of the tail domain of high molecular weight subunits of neurofilaments with the COOH-terminal region of tubulin and its regulation by tau protein kinase II. J Biol Chem 268: 22695-22702.
57. Monteiro MJ, Hoffman PN, Gearhart JD, Cleveland DW, (1990). Expression of NF-L in both neuronal and nonneuronal cells of transgenic mice: increased neurofilament density in axons without affecting caliber. J Cell Biol 111: 1543-1557.
58. Morfini G, Szebenyi G, Brown H, Pant HC, Pigino G, DeBoer S, Beffert U, Brady ST, (2004). A novel CDK5-dependent pathway for regulating GSK3 activity and kinesin-driven motility in neurons. EMBO J 23: 2235-2245.
59. Morooka T, Nishida E, (1998). Requirement of p38 mitogen-activated protein kinase for neuronal differentiation in PC12 cells. J Biol Chem 273: 24285-24288.
60. Motil J, Chan WK, Dubey M, Chaudhury P, Pimenta A, Chylinski TM, Ortiz DT, Shea TB, (2006). Dynein mediates retrograde neurofilament transport within axons and anterograde delivery of NFs from perikarya into axons: regulation by multiple phosphorylation events. Cell Motil Cytoskeleton 63: 266-286.
61. Nguyen MD, Lariviere RC, Julien JP, (2001). Deregulation of Cdk5 in a mouse model of ALS: toxicity alleviated by perikaryal neurofilament inclusions. Neuron 30: 135-147.
62. Nixon RA, Lewis SE, Marotta CA, (1987). Posttranslational modification of neurofilament proteins by phosphate during axoplasmic transport in retinal ganglion cell neurons. J Neurosci 7: 1145-1158.
63. Oblinger MM, (1987). Characterization of posttranslational processing of the mammalian high-molecular-weight neurofilament protein in vivo. J Neurosci 7: 2510-2521.
64. Pant HC, (1988). Dephosphorylation of neurofilament proteins enhances their susceptibility to degradation by calpain. Biochem J 256: 665-668.
65. Pant HC, Shecket G, Gainer H, Lasek RJ, (1978). Neurofilament protein is phosphorylated in the squid giant axon. J Cell Biol 78: R23-R27.
66. Pant HC, Gallant PE, Gainer H, (1986). Characterization of a cyclic nucleotide- and calcium-independent neurofilament protein kinase activity in axoplasm from the squid giant axon. J Biol Chem 261: 2968-2977.
67. Park JE, Lee JA, Park SG, Lee DH, Kim SJ, Kim HJ, Uchida C, Uchida T, Park BC, Cho S, (2012). A critical step for JNK activation: isomerization by the prolyl isomerase Pin1. Cell Death Differ 19: 153-161.
68. Patrick GN, Zukerberg L, Nikolic M, de la Monte S, Dikkes P, Tsai LH, (1999). Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Nature 402: 615-622.
69. Petzold A, (2005). Neurofilament phosphoforms: surrogate markers for axonal injury, degeneration and loss. J Neurol Sci 233: 183-198.
70. Rao MV, Houseweart MK, Williamson TL, Crawford TO, Folmer J, Cleveland DW, (1998). Neurofilament-dependent radial growth of motor axons and axonal organization of neurofilaments does not require the neurofilament heavy subunit (NF-H) or its phosphorylation. J Cell Biol 143: 171-181.
71. Rao MV, Garcia ML, Miyazaki Y, Gotow T, Yuan A, Mattina S, Ward CM, Calcutt NA, Uchiyama Y, Nixon RA, Cleveland DW, (2002). Gene replacement in mice reveals that the heavily phosphorylated tail of neurofilament heavy subunit does not affect axonal caliber or the transit of cargoes in slow axonal transport. J Cell Biol 158: 681-693.
72. Rao MV, Campbell J, Yuan A, Kumar A, Gotow T, Uchiyama Y, Nixon RA, (2003). The neurofilament middle molecular mass subunit carboxyl-terminal tail domains is essential for the radial growth and cytoskeletal architecture of axons but not for regulating neurofilament transport rate. J Cell Biol 163: 1021-1031.
73. Roach PJ, (1991). Multisite and hierarchal protein phosphorylation. J Biol Chem 266: 14139-14142.
74. Roy S, Coffee P, Smith G, Liem RK, Brady ST, Black MM, (2000). Neurofilaments are transported rapidly but intermittently in axons: implications for slow axonal transport. J Neurosci 20: 6849-6861.
75. Rudrabhatla P, Zheng YL, Amin ND, Kesavapany S, Albers W, Pant HC, (2008). Pin1-dependent prolyl isomerization modulates the stress-induced phosphorylation of high molecular weight neurofilament protein. J Biol Chem 283: 26737-26747.
76. Rudrabhatla P, Albers W, Pant HC, (2009). Peptidyl-prolyl isomerase 1 regulates protein phosphatase 2A-meidated topographic phosphorylation of neurofilament proteins. J Neurosci 29: 14869-14480.
77. Sanchez I, Hassinger L, Sihag RK, Cleveland DW, Mohan P, Nixon RA, (2000). Local control of neurofilament accumulation during radial growth of myelinating axons in vivo. Selective role of site-specific phosphorylation. J Cell Biol 151: 1013-1024.
78. Sasaki T, Taoka M, Ishiguro K, Uchida A, Saito T, Isobe T, Hisanaga S, (2002). In vivo and in vitro phosphorylation at Ser-493 in the glutamate (E)-segment of neurofilament-H subunit by glycogen synthase kinase 3beta. J Biol Chem 277: 36032-36039.
79. Sharma P, Veeranna SM, Amin ND, Sihag RK, Grant P, Ahn N, Kulkarni AB, Pant HC, (2002). Phosphorylation of MEK1 by cdk5/p35 down-regulates the mitogen-activated protein kinase pathway. J Biol Chem 277: 528-534.
80. Shea TB, Beermann ML, (1993). Evidence that the monoclonal antibodies SMI-31 and SMI-34 recognize different phosphorylation-dependent epitopes of the murine high molecular mass neurofilament subunit. J Neuroimmunol 44: 117-121.
81. Shea TB, Chan WK, (2008). Regulation of neurofilament dynamics by phosphorylation. Eur J Neurosci 27: 1893-1901.
82. Shea TB, Flanagan LA, (2001). Kinesin, dynein and neurofilament transport. Trends Neurosci 24: 644-648.
83. Shea TB, Yabe J, (2000). Occam's Razor slices through the mysteries of neurofilament axonal transport: can it really be so simple? Traffic 1: 522-523.
84. Shea TB, Jung C, Pant HC, (2003). Does neurofilament phosphorylation regulate axonal transport? Trends Neurosci 26: 397-400.
85. Shea TB, Zheng YL, Ortiz D, Pant HC, (2004a). Cyclin-dependent kinase 5 increases perikaryal neurofilament phosphorylation and inhibits neurofilament axonal transport in response to oxidative stress. J Neurosci Res 76: 795-800.
86. Shea TB, Yabe JT, Ortiz D, Pimenta A, Loomis P, Goldman RD, Amin N, Pant HC, (2004b). Cdk5 regulates axonal transport and phosphorylation of neurofilaments in cultured neurons. J Cell Sci 117: 933-941.
87. Shea TB, Chan WK, Kushkuley J, Lee S, (2009). Organizational dynamics, functions, and pathobiological dysfunctions of neurofilaments. Results Probl Cell Differ 48: 29-45.
88. Shen H, Barry DM, Dale JM, Garcia VB, Calcutt NA, Garcia ML, (2011). Muscle pathology without severe nerve pathology in a new mouse model of Charcot-Marie-Tooth disease type 2E. Hum Mol Genet 20: 2535-2548.
89. Shetty KT, Link WT, Pant HC, (1993). cdc2-like kinase from rat spinal cord specifically phosphorylates KSPXK motifs in neurofilament proteins: isolation and characterization. Proc Natl Acad Sci U S A 90: 6844-6848.
90. Sihag RK, Inagaki M, Yamaguchi T, Shea TB, Pant HC, (2007). Role of phosphorylation on the structural dynamics and function of types III and IV intermediate filaments. Exp Cell Res 313: 2098-2109.
91. Singh TJ, Zaidi T, Grundke-Iqbal I, Iqbal K, (1995). Modulation of GSK-3-catalyzed phosphorylation of microtubule-associated protein tau by non-proline-dependent protein kinases. FEBS Lett 358: 4-8.
92. Sontag E, Hladik C, Montgomery L, Luangpirom A, Mudrak I, Ogris E, White CL III, (2004). Downregulation of protein phosphatase 2A carboxyl methylation and methyltransferase may contribute to Alzheimer disease pathogenesis. J Neuropathol Exp Neurol 63: 1080-1091.
93. Sternberger LA, Sternberger NH, (1983). Monoclonal antibodies distinguish phosphorylated and nonphosphorylated forms of neurofilaments in situ. Proc Natl Acad Sci U S A 80: 6126-6130.
94. Takahashi M, Amin N, Grant P, Pant HC, (1995). P13suc1 associates with a cdc2-like kinase in a multimeric cytoskeletal complex in squid axoplasm. J Neurosci 15: 6222-6229.
95. Tashiro T, Imai R, Komiya Y, (1994). Early effects of beta,beta'-iminodipropionitrile on tubulin solubility and neurofilament phosphorylation in the axon. J Neurochem 63: 291-300.
96. Tomkins J, Usher P, Slade JY, Ince PG, Curtis A, Bushby K, Shaw PJ, (1998). Novel insertion in the KSP region of the neurofilament heavy gene in amyotrophic lateral sclerosis (ALS). Neuroreport 9: 3967-3970.
97. Tortarolo M, Veglianese P, Calvaresi N, Botturi A, Rossi C, Giorgini A, Migheli A, Bendotti C, (2003). Persistent activation of p38 mitogen-activated protein kinase in a mouse model of familial amyotrophic lateral sclerosis correlates with disease progression. Mol Cell Neurosci 23: 180-192.
98. Toyoshima I, Kato K, Sugawara M, Wada C, Masamune O, (1998). Kinesin accumulation in chick spinal axonal swellings with beta,beta'- iminodipropionitrile (IDPN) intoxication. Neurosci Lett 249: 103-106.
99. Tradewell ML, Durham HD, Mushynski WE, Gentil BJ, (2009). Mitochondrial and axonal abnormalities precede disruption of the neurofilament network in a model of Charcot-Marie-Tooth disease type 2E and are prevented by heat shock proteins in a mutant-specific fashion. J Neuropathol Exp Neurol 68: 642-652.
100. Trivedi N, Jung P, Brown A, (2007). Neurofilaments switch between distinct mobile and stationary states during their transport along axons. J Neurosci 27: 507-516.
101. Tu PH, Elder G, Lazzarini RA, Nelson D, Trojanowski JQ, Lee VM, (1995). Overexpression of the human NFM subunit in transgenic mice modifies the level of endogenous NFL and the phosphorylation state of NFH subunits. J Cell Biol 129: 1629-1640.
102. Tytell M, Zackroff RV, Hill WD, (1988). Axonal neurofilaments differ in composition and morphology from those in the soma of the squid stellate ganglion. Cell Motil Cytoskeleton 9: 349-360.
103. Tytell M, Pant HC, Gainer H, Hill WD, (1990). Characterization of the distinctive neurofilament subunits of the soma and axon initial segments in the squid stellate ganglion. J Neurosci Res 25: 153-161.
104. Uchida A, Alami NH, Brown A, (2009). Tight functional coupling of kinesin-1A and dynein motors in the bidirectional transport of neurofilaments. Mol Biol Cell 20: 4997-5006.
105. Veeranna SKT, Link WT, Jaffe H, Wang J, Pant HC, (1995). Neuronal cyclin-dependent kinase-5 phosphorylation sites in neurofilament protein (NF-H) are dephosphorylated by protein phosphatase 2A. J Neurochem 64: 2681-2690.
106. Veeranna AND, Ahn NG, Jaffe H, Winters CA, Grant P, Pant HC, (1998). Mitogen-activated protein kinases (Erk1,2) phosphorylate Lys-Ser-Pro (KSP) repeats in neurofilament proteins NF-H and NF-M. J Neurosci 18: 4008-4021.
107. Veeranna SKT, Takahashi M, Grant P, Pant HC, (2000). Cdk5 and MAPK are associated with complexes of cytoskeletal proteins in rat brain. Brain Res Mol Brain Res 76: 229-236.
108. Veeranna LJH, Pareek TK, Jaffee H, Boland B, Vinod KY, Amin N, Kulkarni AB, Pant HC, Nixon RA, (2008). Neurofilament tail phosphorylation: identity of the RT-97 phosphoepitope and regulation in neurons by cross-talk among proline-directed kinases. J Neurochem 107: 35-49.
109. Veeranna YDS, Lee JH, Vinod KY, Stavrides P, Amin ND, Pant HC, Nixon RA, (2011). Declining phosphatases underlie aging-related hyperphosphorylation of neurofilaments. Neurobiol Aging 32: 2016-2029.
110. Wagner OI, Ascano J, Tokito M, Leterrier JF, Janmey PA, Holzbaur EL, (2004). The interaction of neurofilaments with the microtubule motor cytoplasmic dynein. Mol Biol Cell 15: 5092-5100.
111. Wang L, Ho CL, Sun D, Liem RK, Brown A, (2000). Rapid movement of axonal neurofilaments interrupted by prolonged pauses. Nat Cell Biol 2: 137-141.
112. Williamson TL, Cleveland DW, (1999). Slowing of axonal transport is a very early event in the toxicity of ALS-linked SOD1 mutants to motor neurons. Nat Neurosci 2: 50-56.
113. Xia CH, Roberts EA, Her LS, Liu X, Williams DS, Cleveland DW, Goldstein LS, (2003). Abnormal neurofilament transport caused by targeted disruption of neuronal kinesin heavy chain KIF5A. J Cell Biol 161: 55-66.
114. Xiao S, McLean J, Robertson J, (2006). Neuronal intermediate filaments and ALS: a new look at an old question. Biochim Biophys Acta 1762: 1001-1012.
115. Xu Z, Cork LC, Griffin JW, Cleveland DW, (1993). Increased expression of neurofilament subunit NF-L produces morphological alternations that resemble the pathology of human motor neuron disease. Cell 73: 23-33.
116. Yabe JT, Jung C, Chan WK, Shea TB, (2000). Phospho-dependent association of neurofilament proteins with kinesin in situ. Cell Motil Cytoskeleton 45: 249-262.
117. Yabe JT, Wang FS, Chylinski T, Katchmar T, Shea TB, (2001a). Selective accumulation of the high molecular weight neurofilament subunit within the distal region of growing axonal neurites. Cell Motil Cytoskeleton 50: 1-12.
118. Yabe JT, Chylinski T, Wang FS, Pimenta A, Kattar SD, Linsley MD, Chan WK, Shea TB, (2001b). Neurofilaments consist of distinct populations that can be distinguished by C-terminal phosphorylation, bundling, and axonal transport rate in growing axonal neurites. J Neurosci 21: 2195-2205.
119. Yuan A, Nixon RA, Rao MV, (2006a). Deleting the phosphorylated tail domain of the neurofilament heavy subunit does not alter neurofilament transport rate in vivo. Neurosci Lett 393: 264-268.
120. Yuan A, Rao MV, Sasaki T, Chen Y, Kumar A, Veeranna LRK, Eyer J, Peterson AC, Julien JP, Nixon RA, (2006b). Alpha-internexin is structurally and functionally associated with the neurofilament triplet proteins in the mature CNS. J Neurosci 26: 10006-10019.
121. Zheng YL, Li BS, Veeranna PHC, (2003). Phosphorylation of the head domain of neurofilament protein (NF-M): a factor regulating topographic phosphorylation of NF-M tail domain KSP sites in neurons. J Biol Chem 278: 24026-24032.
122. Zhou J, Wang H, Feng Y, Chen J, (2010). Increased expression of cdk5/p25 in N2a cells leads to hyperphosphorylation and impaired axonal transport of neurofilament proteins. Life Sci 86: 532-537.
123. Zhu Q, Couillard-Després S, Julien J-P, (1997). Delayed maturation of regenerating myelinated axons in mice lacking neurofilaments. Exp Neurol 148: 299-316.
124. Zuchner S, Vorgerd M, Sindern E, Schroder JM, (2004). The novel neurofilament light (NEFL) mutation Glu397Lys is associated with a clinically and morphologically heterogeneous type of Charcot-Marie-Tooth neuropathy. Neuromuscul Disord 14: 147-157.