Effect of phosphorylation on 68 KDa neurofilament subunit protein assembly by the cyclic AMP dependent protein kinase in vitro

Nakamura, Yu; Takeda, Masatoshi; Angelides, Kimon J.; Tanaka, Toshihisa; Tada, Kazuya; Nishimura, Tsuyoshi

doi:10.1016/0006-291x(90)90394-3

Cited by 75 publications

(54 citation statements)

References 12 publications

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“…197 Secondary messenger cascades activate protein kinases, phospholipases, and proteases, which within 6 h leads to either neurofilament instability via phosphorylation or neurofilament collapse via calpain-mediated proteolysis of side-arms. 198 Ca 2þ -mediated microtubule disassembly ensues, 199 and cytoskeletal disorganization often persists, 200 with silver staining used to visualize the punctate structures and argyrophilic fibers that are observed. Proteins accumulate, leading to multifocal axonal swellings that hinder axonal transport, 201 often detected as accumulations of amyloid precursor protein (APP).…”

Section: 180mentioning

confidence: 99%

Repeated mild traumatic brain injury: potential mechanisms of damage

2016

Cell Transplant

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Mild traumatic brain injury (mTBI) represents a significant public healthcare concern, accounting for the majority of all head injuries. While symptoms are generally transient, some patients go on to experience long-term cognitive impairments and additional mild impacts can result in exacerbated and persisting negative outcomes. To date, studies using a range of experimental models have reported chronic behavioral deficits in the presence of axonal injury and inflammation following repeated mTBI; assessments of oxidative stress and myelin pathology have thus far been limited. However, some models employed induced acute focal damage more suggestive of moderate-severe brain injury and are therefore not relevant to repeated mTBI. Given that the nature of mechanical loading in TBI is implicated in downstream pathophysiological changes, the mechanisms of damage and chronic consequences of single and repeated closed-head mTBI remain to be fully elucidated. This review covers literature on potential mechanisms of damage following repeated mTBI, integrating known mechanisms of pathology underlying moderate-severe TBIs, with recent studies on adult rodent models relevant to direct impact injuries rather than blast-induced damage. Pathology associated with excitotoxicity and cerebral blood flow-metabolism uncoupling, oxidative stress, cell death, blood-brain barrier dysfunction, astrocyte reactivity, microglial activation, diffuse axonal injury, and dysmyelination is discussed, followed by a summary of functional deficits and preclinical assessments of therapeutic strategies. Comprehensive characterization of the pathology underlying delayed and persisting deficits following repeated mTBI is likely to facilitate further development of therapeutic strategies to limit long-term sequelae.

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Section: 180mentioning

confidence: 99%

Repeated mild traumatic brain injury: potential mechanisms of damage

2016

Cell Transplant

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“…59 Although the role of phosphorylated NF-L on NMDA receptor expression has not been studied, NF-L phosphorylation prevents subsequent NF assembly and induces disassembly in existing NF-L formed filaments. [60][61][62] Nixon and Shiag 63 suggest that in postmitotic cells, NF-L phosphorylation prevents polymerization immediately after synthesis (that is increased turnover)-allowing proper integration of NF-M and -H subunits. Therefore, decreased NF-L phosphorylation may be expected to increase NF assembly and stabilize existing filaments-thereby stabilizing NF-L/NR1 interactions.…”

Section: Structuralmentioning

confidence: 99%

Integrative proteomic analysis of the nucleus accumbens in rhesus monkeys following cocaine self-administration

2008

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The reinforcing effects and long-term consequences of cocaine self-administration have been associated with brain regions of the mesolimbic dopamine pathway, namely the nucleus accumbens (NAc). Studies of cocaine-induced biochemical adaptations in rodent models have advanced our knowledge; however, unbiased detailed assessments of intracellular alterations in the primate brain are scarce, yet essential, to develop a comprehensive understanding of cocaine addiction. To this end, two-dimensional difference in gel electrophoresis (2D-DIGE) was used to compare changes in cytosolic protein abundance in the NAc between rhesus monkeys selfadministering cocaine and controls. Following image normalization, spots with significantly differential image intensities (P < 0.05) were identified, excised, trypsin digested and analyzed by matrix-assisted laser-desorption ionization time-of-flight time-of-flight (MALDI-TOF-TOF). In total, 1098 spots were subjected to statistical analysis with 22 spots found to be differentially abundant of which 18 proteins were positively identified by mass spectrometry. In addition, approximately 1000 protein spots were constitutively expressed of which 21 proteins were positively identified by mass spectrometry. Increased levels of proteins in the cocaine-exposed monkeys include glial fibrillary acidic protein, syntaxin-binding protein 3, protein kinase C isoform, adenylate kinase isoenzyme 5 and mitochondrial-related proteins, whereas decreased levels of proteins included β-soluble N-ethylmaleimide-sensitive factor attachment protein and neural and non-neural enolase. Using a complimentary proteomics approach, the differential expression of phosphorylated proteins in the cytosolic fraction of these subjects was examined. Two-dimensional gel electrophoresis (2DGE) was followed by gel staining with Pro-Q Diamond phosphoprotein gel stain, enabling differentiation of approximately 150 phosphoprotein spots between the groups. Following excision and trypsin digestions, MALDI-TOF-TOF was used to confirm the identity of 15 cocaine-altered phosphoproteins. Significant increased levels were detected for γ-aminobutyric acid type A receptor-associated protein 1, 14-3-3 γ-protein, glutathione S-transferase and brain-type aldolase, whereas significant decreases were observed for β-actin, Rab GDP-dissociation inhibitor, guanine deaminase, peroxiredoxin 2 isoform b and Results from these studies indicate coordinated dysregulation of proteins related to cell structure, signaling, metabolism and mitochondrial function. These data extend and compliment previous studies of cocaine-induced biochemical alterations in human post-mortem brain tissue, using an animal model that closely recapitulates the human condition and provide new insight into the molecular basis of the disease and potential targets for pharmacotherapeutic intervention.

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“…The mechanism of NF-assembly therefore remains to be elucidated. It has been shown in vitro that phosphorylation of NF-L by the catalytic subunit of cAMP-dependent protein kinase (A-kinase) and protein kinase C inhibited its polymerization into long filaments and also depolymerized filaments (Gonda et al, 1990;Nakamura et al, 1990). The major A-kinase phosphorylation site has been identified as Ser-55 in the amino-terminal head domain of NF-L (Sihag and Nixon, 1991).…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation of native and reassembled neurofilaments composed of NF-L, NF-M, and NF-H by the catalytic subunit of cAMP-dependent protein kinase.

Hisanaga

Matsuoka

Nishizawa

et al. 1994

MBoC

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native NF was nearly the same as that of purified NF-L. However, phosphorylation did not cause the native NFs to disassemble into oligomers, as was the case for purified NF-L. Instead, partial fragmentation was detected in sedimentation experiments and by electron microscopic observations. This is probably not due to the presence of the three NF subunits in NF or to differences in phosphorylation sites because reassembled NF containing all three NF subunits were disassembled into oligomeric forms by phosphorylation with A-kinase and the phosphorylation by A-kinase occurred at the head domain of NF-L whether NF were native or reassembled. Disassembling intermediates of reassembled NF containing all three NF subunits were somewhat different from disassembling intermediates of NF-L. Thinning and loosening of filaments was frequently observed preceding complete disassembly. From the fact that the thinning was also observed in the native filaments phosphorylated by A-kinase, it is reasonable to propose the native NF is fragmented through a process of thinning that is stimulated by phosphorylation in the head domain of the NF subunits.

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Effect of phosphorylation on 68 KDa neurofilament subunit protein assembly by the cyclic AMP dependent protein kinase in vitro

Cited by 75 publications

References 12 publications

Repeated mild traumatic brain injury: potential mechanisms of damage

Repeated mild traumatic brain injury: potential mechanisms of damage

Integrative proteomic analysis of the nucleus accumbens in rhesus monkeys following cocaine self-administration

Phosphorylation of native and reassembled neurofilaments composed of NF-L, NF-M, and NF-H by the catalytic subunit of cAMP-dependent protein kinase.

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