Microtubule‐associated proteins as direct crosslinkers of actin filaments and microtubules

Mohan, Renu; John, Annie

doi:10.1002/iub.1384

Cited by 95 publications

(79 citation statements)

References 77 publications

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“…Moreover, binding to microtubules is in equilibrium with the interactions of MAPs with other components of the cytoskeleton. Phosphorylation in MTBRs promotes MAP2c localization to actin-rich regions of neurons (28), with a direct impact on neuronal development and plasticity (19,61,62). It is evident that the kinetics of phosphorylation is an important factor in determining the balance of the aforementioned effects and contributes to the specificity of the control of microtubule stability by Tau and MAP2c under different physiological conditions and in different regions of neurons (8).…”

Section: Phosphorylation Of Map2c and Interaction With 14-3-3mentioning

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

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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 ...

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Section: Phosphorylation Of Map2c and Interaction With 14-3-3mentioning

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

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“…MAP-2 is an important structural and functional protein found in the neuron bodies and dendrites for maintaining microtubule stability and nerve regeneration (Mohan and John, 2015). Our results showed YGPs increased the expression of MAP-2 in the brain and spinal cord of EAE mice and the increase in MAP-2 with YGPs thereby indicates its effects of promoting nerve regeneration.…”

Section: Discussionmentioning

confidence: 80%

You-Gui pills promote nerve regeneration by regulating netrin1, DCC and Rho family GTPases RhoA, Racl, Cdc42 in C57BL/6 mice with experimental autoimmune encephalomyelitis

Liu

Chen

et al. 2016

Journal of Ethnopharmacology

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“…Aurora A regulates centrosome maturation, entry into mitosis, formation and function of the bipolar spindle, microtubule dynamics, and control of cell polarity [18]. Microtubule-associated protein 4 is a major non-neuronal microtubule-associated protein that regulates microtubule polymerization and cellular morphology [19]. Thus, it is tempting to speculate that ALG-2 may regulate cytoskeletal rearrangement through interactions with specific cytoskeleton-associated proteins.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis-linked gene 2 promotes breast cancer growth and metastasis by regulating the cytoskeleton

Qin

Zhou

et al. 2016

Oncotarget

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Breast cancer is the most prevalent cancer in women. Although it begins as local disease, breast cancer frequently metastasizes to the lymph nodes and distant organs. Therefore, novel therapeutic targets are needed for the management of this disease. Apoptosis-linked gene 2 (ALG-2) is a calcium-binding protein crucial for diverse physiological processes and has recently been implicated in cancer development. However, it remains unclear whether this protein is involved in the pathogenesis of breast cancer. Here, we demonstrate that the expression of ALG-2 is significantly upregulated in breast cancer tissues and is correlated with clinicopathological characteristics indicative of tumor malignancy. Our data further show that ALG-2 stimulates breast cancer growth and metastasis in mice. ALG-2 also promotes breast cancer cell proliferation, survival, and motility in vitro. Mechanistic data reveal that ALG-2 disrupts the localization of centrosome proteins, resulting in spindle multipolarity and chromosome missegregation. In addition, ALG-2 drives the polarization and migration of breast cancer cells by facilitating the rearrangement of microtubules and microfilaments. These findings reveal a critical role for ALG-2 in the pathogenesis of breast cancer and have important implications for its diagnosis and therapy.

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Microtubule‐associated proteins as direct crosslinkers of actin filaments and microtubules

Cited by 95 publications

References 77 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

You-Gui pills promote nerve regeneration by regulating netrin1, DCC and Rho family GTPases RhoA, Racl, Cdc42 in C57BL/6 mice with experimental autoimmune encephalomyelitis

Apoptosis-linked gene 2 promotes breast cancer growth and metastasis by regulating the cytoskeleton

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