Cytoskeletal mechanisms of neuronal degeneration

Brandt, Roland

doi:10.1007/s004410000334

Cited by 48 publications

(28 citation statements)

References 111 publications

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“…Ancient and common pathways may function to establish and maintain membrane-cytoskeletal dynamics in different cell types and organisms. Fourteen percent of the mammalian proteins identified in this study are implicated in human diseases with membrane-cytoskeletal pathologies, such as Huntington's disease, deafness, sclerosis, melanoma, and leukemia (62)(63)(64)(65)(66), suggesting that functional characterization of cell division proteins may help to identify mammalian disease loci and characterize pathologies. The utilization of common components in diverse dynamic membrane cytoskeletal events in the cleavage furrow, the germline, and neurons indicates ancient mechanisms mediating cell division and complex morphogenetic cellular processes critical in human development and disease.…”

Section: Functional Analysis Of Midbody Proteins Reveals Conserved Momentioning

confidence: 92%

Dissection of the Mammalian Midbody Proteome Reveals Conserved Cytokinesis Mechanisms

Skop

Liu

Yates

et al. 2004

Science

468

509

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Cytokinesis is the essential process that partitions cellular contents into daughter cells. To identify and characterize cytokinesis proteins rapidly, we used a functional proteomic and comparative genomic strategy. Midbodies were isolated from mammalian cells, proteins were identified by multidimensional protein identification technology (MudPIT), and protein function was assessed in Caenorhabditis elegans. Of 172 homologs disrupted by RNA interference, 58% displayed defects in cleavage furrow formation or completion, or germline cytokinesis. Functional dissection of the midbody demonstrated the importance of lipid rafts and vesicle trafficking pathways in cytokinesis, and the utilization of common membrane cytoskeletal components in diverse morphogenetic events in the cleavage furrow, the germline, and neurons.A critical phase of cell division occurs just after segregation of the duplicated genome, when the chromosomes, cytoplasm, and organelles are partitioned to two daughter cells in a process termed cytokinesis. In animal cells, this event is driven by a cortical contraction that pinches the cell into two and requires coordination of the mitotic spindle, actin cytoskeleton, and plasma membrane. Failures in cytokinesis can cause cell death and age-related disorders or lead to a genome amplification characteristic of many cancers (1, 2). To understand the mechanisms of cytokinesis, the identity and function of proteins comprising the structures involved must be ascertained. We combined several approaches to obtain and study conserved and relevant factors, capitalizing on recent advances in proteomics and functional genomics.To identify proteins involved in cytokinesis, we examined a transient "organelle-like" structure called the midbody, first described by Flemming in 1891 as the remnant of cell division just prior to abscission (3, 4). Morphologically, the mammalian midbody is a dense structure containing microtubules derived from the spindle midzone tightly bundled by the cytokinetic furrow (5). Although no clear function has been ascribed to the midbody, it is

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Section: Functional Analysis Of Midbody Proteins Reveals Conserved Momentioning

confidence: 92%

Dissection of the Mammalian Midbody Proteome Reveals Conserved Cytokinesis Mechanisms

Skop

Liu

Yates

et al. 2004

Science

468

509

View full text Add to dashboard Cite

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“…The modifications observed on a number of cytoskeletal proteins may also have implications in disease because cytoskeleton integrity is essential for normal cell functions; abnormalities in cytoskeleton organization have been observed in many diseases, especially neurodegenerative diseases (59).…”

Section: Discussionmentioning

confidence: 99%

Endogenous 3,4-Dihydroxyphenylalanine and Dopaquinone Modifications on Protein Tyrosine

Zhang

Monroe

Chen

et al. 2010

Molecular & Cellular Proteomics

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Oxidative modifications of protein tyrosines have been implicated in multiple human diseases. Among these modifications, elevations in levels of 3,4-dihydroxyphenylalanine (DOPA), a major product of hydroxyl radical addition to tyrosine, has been observed in a number of pathologies. Here we report the first proteome survey of endogenous site-specific modifications, i.e. DOPA and its further oxidation product dopaquinone in mouse brain and heart tissues. Results from LC-MS/MS analyses included 50 and 14 DOPA-modified tyrosine sites identified from brain and heart, respectively, whereas only a few nitrotyrosine-containing peptides, a more commonly studied marker of oxidative stress, were detectable, suggesting the much higher abundance for DOPA modification as compared with tyrosine nitration. Moreover, 20 and 12 dopaquinone-modified peptides were observed from brain and heart, respectively; nearly one-fourth of these peptides were also observed with DOPA modification on the same sites. For both tissues, these modifications are preferentially found in mitochondrial proteins with metal binding properties, consistent with metal-catalyzed hydroxyl radical formation from mitochondrial superoxide and hydrogen peroxide. These modifications also link to a number of mitochondrially associated and other signaling pathways. Furthermore, many of the modification sites were common sites of previously reported tyrosine phosphorylation, suggesting potential disruption of signaling pathways. Collectively, the results suggest that these modifications are linked with mitochondrially derived oxidative stress and may serve as sensitive markers for disease pathologies. Molecular & Cellular Proteomics 9:1199 -1208, 2010.

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“…The cytoskeleton is affected by stress [42,70], and heat shock or other stressors can cause the collapse of the filament network, alter the MT properties, also through modulation of the phosphorylation of microtubule-associated proteins, including tau [129], or induce a loss of stress fibers. The integrity of the cytoskeletal network is disturbed in many neurodegenerative disorders (for review see [130]); abnormalities in the organization of the filament system often are histopathological hallmarks and may provide diagnostic markers for different stages of neurodegeneration [131]. Filamentous inclusions, which are observed in a variety of neurodegenerative disorders in nerve cells and glia [132], often contain cytoskeletal proteins and stain with antibodies against ubiquitin and a variety of HSPs (for review see [43,70,133,134]).…”

Section: The Cytoskeleton and Cytoplasmic Inclusionsmentioning

confidence: 99%

Stress proteins in neural cells: functional roles in health and disease

Richter‐Landsberg¹,

Goldbaum²

2003

Cellular and Molecular Life Sciences (CMLS)

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Heat shock proteins (HSPs) or stress proteins participate in protein synthesis, protein folding, transport and translocalization processes. Stress situations trigger a heat shock response leading to their induction. Similarly, they can be upregulated by impairment of the proteasomal degradation pathway. The upregulation of stress proteins is an important step in prevention of protein aggregation and misfolding after stress, and also is essential during development and differentiation. A number of HSPs are constitutively or inducibly expressed in the nervous system and connected to protection of nerve cells and glia. The cytoskeleton is affected by stress, and HSPs have been shown to interact with the cytoskeleton in normal cells and to assist proper assembly, spatial organization and cross-linking properties. The integrity of the cytoskeleton is disturbed in many neurodegenerative disorders, and filamentous cytoplasmic inclusion bodies, containing a variety of HSPs, are observed. This review summarizes the recent literature on the presence and induction of HSPs in neural cells, and their possible functional roles in health and disease are discussed.

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Cytoskeletal mechanisms of neuronal degeneration

Cited by 48 publications

References 111 publications

Dissection of the Mammalian Midbody Proteome Reveals Conserved Cytokinesis Mechanisms

Dissection of the Mammalian Midbody Proteome Reveals Conserved Cytokinesis Mechanisms

Endogenous 3,4-Dihydroxyphenylalanine and Dopaquinone Modifications on Protein Tyrosine

Stress proteins in neural cells: functional roles in health and disease

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