Intermediate filament-associated cytolinker plectin 1c destabilizes microtubules in keratinocytes

Valencia, Rocio G.; Walko, Gernot; Janda, Lubomír; Nováček, Jiří; Mihailovska, Eva; Reipert, Siegfried; Andrä-Marobela, Kerstin; Wiche, Gerhard

doi:10.1091/mbc.e12-06-0488

Cited by 41 publications

(63 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Co-sedimentation assays were adapted from Valencia et al (76). Samples of 5 M porcine brain tubulin in 30 l of tubulin buffer (80 mM PIPES, pH 6.9, 2 mM MgCl 2 , and 0.5 mM EGTA) were polymerized by the addition of 2 M MAP2c and incubated for 15 min at 37°C.…”

Section: Microtubular Co-sedimentation Assaymentioning

confidence: 99%

Quantitative mapping of microtubule-associated protein 2c (MAP2c) phosphorylation and regulatory protein 14-3-3ζ-binding sites reveals key differences between MAP2c and its homolog Tau

Jansen

Melková

Trošanová

et al. 2017

Journal of Biological Chemistry

View full text Add to dashboard Cite

Edited by Norma AllewellMicrotubule-associated protein 2c (MAP2c) is involved in neuronal development and is less characterized than its homolog Tau, which has various roles in neurodegeneration. Using NMR methods providing single-residue resolution and quantitative comparison, we investigated molecular interactions important for the regulatory roles of MAP2c in microtubule dynamics. We found that MAP2c and Tau significantly differ in the position and kinetics of sites that are phosphorylated by cAMP-dependent protein kinase (PKA), even in highly homologous regions. We determined the binding sites of unphosphorylated and phosphorylated MAP2c responsible for interactions with the regulatory protein 14-3-3 . Differences in phosphorylation and in charge distribution between MAP2c and Tau suggested that both MAP2c and Tau respond to the same signal (phosphorylation by PKA) but have different downstream effects, indicating a signaling branch point for controlling microtubule stability. Although the interactions of phosphorylated Tau with 14-3-3 are supposed to be a major factor in microtubule destabilization, the binding of 14-3-3 to MAP2c enhanced by PKA-mediated phosphorylation is likely to influence microtubule-MAP2c binding much less, in agreement with the results of our tubulin co-sedimentation measurements. The specific location of the major MAP2c phosphorylation site in a region homologous to the muscarinic receptor-binding site of Tau suggests that MAP2c also may regulate processes other than microtubule dynamics.Cytoskeletal microtubule-associated proteins (MAPs) 3 are proteins of critical importance for regulating the stability and dynamics of microtubules (1). MAP2 and Tau represent MAP subfamilies expressed in neurons; MAP2 is localized in dendrites, whereas Tau is found mainly in axons (2). Tau and MAP2 belong to the class of intrinsically disordered proteins (IDPs), which lack a unique structure and which exist in multiple, quickly interconverting conformations (3-7). NMR is the method of choice for structural investigation of this type of protein. Tau and MAP2 differ in their N-terminal projection domains, which contain acidic and proline-rich subdomains, whereas the C-terminal parts, containing the microtubulebinding domain (MTBD) and the C-terminal region, are homologous (8). Tau is expressed in several splice variants. The human brain isoforms differ in the number of microtubulebinding regions (MTBRs) in the C-terminal portion and in the presence of two inserts near the N terminus. For the sake of simplicity, only the 441-residue variant lacking exons 6, 8, and 10 (9) is discussed in this paper. This variant has been studied in detail and was shown to form paired helical filaments and neurofibillary tangles in brains of patients suffering from Alzheimer's disease (10). The MAP2 family is composed of two high-molecular-weight proteins, MAP2a and MAP2b, each consisting of 1830 amino acids, and two low-molecular-weight proteins, MAP2c and MAP2d, consisting of 467 and 498 amino acids, respectively. The ...

show abstract

Section: Microtubular Co-sedimentation Assaymentioning

confidence: 99%

Quantitative mapping of microtubule-associated protein 2c (MAP2c) phosphorylation and regulatory protein 14-3-3ζ-binding sites reveals key differences between MAP2c and its homolog Tau

Jansen

Melková

Trošanová

et al. 2017

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…However, despite expectations that may have been raised by these studies, it has never been shown that plectinmediated interactions of IFs contribute to the stability of MT networks; neither has convincing evidence been reported that such interactions are instrumental in aligning or guiding MTs and IFs along each other, a function likely provided by other proteins, such as the tumor suppressor APC [60 ]. On the contrary, plectin deficiency, specifically of isoform P1c, leads to increased formation and stability of MTs in keratinocytes, myofibers, neurons, and (tendentiously) fibroblasts ( [51,61 ], and unpublished data). These observations are consistent with the idea that consolidation of IF structures through plectin favors the dynamic state of MTs and thus counteracts their stabilization, similar to the situation with actin filaments.…”

Section: If-networking Fosters Mt Dynamicsmentioning

confidence: 92%

“…Reported binding partners include actin, integrin-b4, nesprin, dystrophin, utrophin, vimentin, calmodulin, and PIP 2 , with more to expect. The SH3 domain of plectin mediates destabilization of MTs [61 ]. With a visualized length of 200 nm, plectin has the longest rod domain of all plakins.…”

Section: Hemidesmosomes and The Role Of P1amentioning

confidence: 99%

Networking and anchoring through plectin: a key to IF functionality and mechanotransduction

Wiche¹,

Osmanagic‐Myers²,

Castañón³

2015

Current Opinion in Cell Biology

Self Cite

105

View full text Add to dashboard Cite

“…Finally, it should be noticed that plec1-1 and plec1-2 siRNAs treatments, after 72 h, triggered diminished growth rate of cells (20 -30% decrease of cell number in comparison with control siRNA due to cell death linked to aberrant mitosis; this has been reported for another plectin isoform (48)). …”

Section: Methodsmentioning

confidence: 60%

The Bin/Amphiphysin/Rvs (BAR) Domain Protein Endophilin B2 Interacts with Plectin and Controls Perinuclear Cytoskeletal Architecture

Vannier

Pesty

San-Roman³

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Endophilin B2 is a BAR protein of previously unidentified function. Results: Endophilin B2 interacts directly with plectin 1 and controls the perinuclear vimentin network. Conclusion:The endophilin B2-plectin 1 complex functions as an anchoring device via BAR-mediated membrane binding activity. Significance: Our data unravel a novel activity of a BAR protein that does not involve membrane deforming activity supporting membrane trafficking.

show abstract

Intermediate filament-associated cytolinker plectin 1c destabilizes microtubules in keratinocytes

Cited by 41 publications

References 75 publications

Quantitative mapping of microtubule-associated protein 2c (MAP2c) phosphorylation and regulatory protein 14-3-3ζ-binding sites reveals key differences between MAP2c and its homolog Tau

Quantitative mapping of microtubule-associated protein 2c (MAP2c) phosphorylation and regulatory protein 14-3-3ζ-binding sites reveals key differences between MAP2c and its homolog Tau

Networking and anchoring through plectin: a key to IF functionality and mechanotransduction

The Bin/Amphiphysin/Rvs (BAR) Domain Protein Endophilin B2 Interacts with Plectin and Controls Perinuclear Cytoskeletal Architecture

Contact Info

Product

Resources

About