Dynamics of neuronal intermediate filaments: A developmental perspective

Nixon, Ralph A.; Shea, Thomas B.

doi:10.1002/cm.970220202

Cited by 216 publications

(165 citation statements)

References 104 publications

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“…We have proposed that transient head domain phosphorylation of NF-L and presumably of NF-M by PKA occurs within neuronal cell bodies to prevent NF assembly and tail domain phosphorylation by proline-directed kinases (8,32). As partially assembled subunits enter the axon hillock and proximal axon, the hypothesis poses dephosphorylation of head domain sites, followed by NF assembly within the axon, where KSP repeats in C-terminal tail domains of NF-M and NF-H are extensively phosphorylated (6,7).…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that this transient head domain phosphorylation in cell bodies inhibits NF polymerization and filament formation (4,21). Extensive phosphorylation of KSP repeats in the tail domain of NF-M and NF-H occurs primarily in axons (7,22,23). These result in sidearm formation, increased inter-neurofilament spacing, radial growth of axons, and increased conduction velocity (24 -26).…”

Section: Neurofilament (Nf)mentioning

confidence: 99%

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Phosphorylation of the Head Domain of Neurofilament Protein (NF-M)

Zheng

Veeranna³

et al. 2003

Journal of Biological Chemistry

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In neurons the phosphorylation of neurofilament (NF) proteins NF-M and NF-H is topographically regulated.Although kinases and NF subunits are synthesized in cell bodies, extensive phosphorylation of the KSP repeats in tail domains of NF-M and NF-H occurs primarily in axons. The nature of this regulation, however, is not understood. As obligate heteropolymers, NF assembly requires interactions between the core NF-L with NF-M or NF-H subunits, a process inhibited by NF head domain phosphorylation. Phosphorylation of head domains at protein kinase A (PKA)-specific sites seems to occur transiently in cell bodies after NF subunit synthesis. We have proposed that transient phosphorylation of head domains prevents NF assembly in the soma and inhibits tail domain phosphorylation; i.e. assembly and KSP phosphorylation in axons depends on prior dephosphorylation of head domain sites. Deregulation of this process leads to pathological accumulations of phosphorylated NFs in the soma as seen in some neurodegenerative disorders. To test this hypothesis, we studied the effect

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Section: Discussionmentioning

confidence: 99%

Section: Neurofilament (Nf)mentioning

confidence: 99%

Phosphorylation of the Head Domain of Neurofilament Protein (NF-M)

Zheng

Veeranna³

et al. 2003

Journal of Biological Chemistry

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“…Neurofilaments are composed of three subunits, identified as light (NF-L), medium (NF-M), and heavy (NF-H), which assemble in a 6:2:1 ratio to form long macromolecular filaments (Nixon and Lewis, 1986;Nixon and Shea, 1992). Consequently, NF-L is more abundant than the other two subunits in neurons.…”

mentioning

confidence: 99%

Superoxide Dismutase Catalyzes Nitration of Tyrosines by Peroxynitrite in the Rod and Head Domains of Neurofilament‐L

Crow

Ye²,

Strong

et al. 1997

Journal of Neurochemistry

238

123

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Superoxide dismutase (SOD) catalyzes the nitration of specific tyrosine residues in proteins by peroxynitrite (ONOO), which may be the damaging gain-offunction resulting from mutations to SOD associated with familial amyotrophic lateral sclerosis (ALS). We found that disassembled neurofilament-L (light subunit) was more susceptible to tyrosine nitration catalyzed by SOD in vitro. Neurofilament-L was selectively nitrated compared with the majority of other proteins present in brain homogenates. Assembled neurofilament-L was more resistant to nitration, suggesting that the susceptible tyrosine residues were protected by intersubunit contacts in assembled neurofilaments. Electrospray mass spectrometry of trypsin-digested neurofilament-L showed that tyrosine 17 in the head region and tyrosines 138, 177, and 265 in a-helical coil regions of the rod domain of neurofilament-L were particularly susceptible to SOD-catalyzed nitration. Nitrated neurofilament-L inhibited the assembly of unmodified neurofilament subunits, suggesting that the affected tyrosines are located in regions important for intersubunit contacts. Neurofilaments are major structural proteins expressed in motor neurons and known to be important for their survival in vivo. We suggest that SODcatalyzed nitration of neurofilament-L may have a significant role in the pathogenesis of ALS.

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“…20 It has been reported to express in the germinal matrix layer cells and radial fibers during the neuronal migration and be gradually replaced by vimentin. 21,22 D2-40 immunoreactivity was intensely found in the germinal matrix layer cells and radial fibers in 6 gestational weeks and thereafter it became restricted in and around the germinal matrix layer gradually. In the germinal matrix layer, the cell surface of ependymal cells, neural stem/progenitor cells and glioblasts were intensely immunoreactive with D2-40 during 8-30 gestational weeks.…”

Section: Discussionmentioning

confidence: 92%

D2-40 antibody immunoreactivity in developing human brain, brain tumors and cultured neural cells

et al. 2006

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D2-40 antibody is raised against an oncofetal antigen, the M2A antigen. It has been used as a marker for lymphatic endothelium as well as mesothelioma and cerebellar hemangioblastoma. We demonstrate here that positive D2-40 immunoreactivity was found in the developing cerebrum, particularly in the germinal matrix layer, immature ependyma, choroid plexus and meninges. In the developing cerebellum, positive D2-40 immunoreactivity was found in the external granular layer particularly of the outer portion and the Purkinje cell layer as well as meninges. Some brain tumors such as anaplastic ependymoma, some medulloblastomas, glioblastoma, pineal germinoma, craniopharyngioma, choroid plexus papilloma, choroid plexus carcinoma, and meningioma showed positive immunoreactivity with D2-40. Therefore, D2-40 antibody is considered a useful marker for research on developing brain and diagnosis of brain tumors, differentiation between choroid plexus carcinoma and metastatic carcinoma. In addition, on cultured human neural cells, D2-40 immunoreactivity was found in nestin-positive neural stem/progenitor cells and neuronal lineage cells. As D2-40 antibody recognizes cell surface antigen M2A, it might be a candidate cell surface marker for isolation of human neural stem cells/ neuronal lineage cells in the fluorescence-activated cell sorting technique.

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Dynamics of neuronal intermediate filaments: A developmental perspective

Cited by 216 publications

References 104 publications

Phosphorylation of the Head Domain of Neurofilament Protein (NF-M)

Phosphorylation of the Head Domain of Neurofilament Protein (NF-M)

Superoxide Dismutase Catalyzes Nitration of Tyrosines by Peroxynitrite in the Rod and Head Domains of Neurofilament‐L

D2-40 antibody immunoreactivity in developing human brain, brain tumors and cultured neural cells

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