Regulated Association of Microtubule-associated Protein 2 (MAP2) with Src and Grb2: Evidence for MAP2 as a Scaffolding Protein

Lim, Rita W.L.; Halpain, Shelley

doi:10.1074/jbc.m001887200

Cited by 79 publications

(70 citation statements)

References 72 publications

(70 reference statements)

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“…It is tempting to speculate that recruitment of EB3 to MAP2-decorated mi- Illenberger et al, 1996;Lim and Halpain, 2000;Zhong et al, 2009). Our data also indicate that EB3 has a higher affinity for dephosphorylated MAP2.…”

Section: Stable Map2-decorated Microtubules Trap Eb3mentioning

confidence: 72%

NMDA Receptor Activation Suppresses Microtubule Growth and Spine Entry

Kapitein

Yau²,

Gouveia³

et al. 2011

J. Neurosci.

106

105

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Dynamic microtubules are important to maintain neuronal morphology and function, but whether neuronal activity affects the organization of dynamic microtubules is unknown. Here, we show that a protocol to induce NMDA-dependent long-term depression (LTD) rapidly attenuates microtubule dynamics in primary rat hippocampal neurons, removing the microtubule-binding protein EB3 from the growing microtubule plus-ends in dendrites. This effect requires the entry of calcium and is mediated by activation of NR2B-containing NMDA-type glutamate receptor. The rapid NMDA effect is followed by a second, more prolonged response, during which EB3 accumulates along MAP2-positive microtubule bundles in the dendritic shaft. MAP2 is both required and sufficient for this activity-dependent redistribution of EB3. Importantly, NMDA receptor activation suppresses microtubule entry in dendritic spines, whereas overexpression of EB3-GFP prevents NMDA-induced spine shrinkage. These results suggest that short-lasting and long-lasting changes in dendritic microtubule dynamics are important determinants for NMDA-induced LTD.

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Section: Stable Map2-decorated Microtubules Trap Eb3mentioning

confidence: 72%

NMDA Receptor Activation Suppresses Microtubule Growth and Spine Entry

Kapitein

Yau²,

Gouveia³

et al. 2011

J. Neurosci.

106

105

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“…The tumor suppressor protein p53 also uses MT tracks to migrate to the nucleus (4). Various protein kinases such as the MAP kinase kinase kinase MLK2 (5) or the MAP kinases ERK1 and ERK2 (6) were also shown to interact or to colocalize with MTs or with microtubule-associated proteins (7).…”

mentioning

confidence: 99%

STAT5B-mediated Growth Hormone Signaling Is Organized by Highly Dynamic Microtubules in Hepatic Cells

Phung-Koskas

Pilon

Poüs

et al. 2005

Journal of Biological Chemistry

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In the last decade, the notion that microtubules are critical to the spatial organization of signal transduction and contribute to the transmission of signals to downstream targets has been proposed. Because the STAT5B transduction and transcription factor is the major STAT protein activated by growth hormone stimulation in hepatocytes and is a crossroads between many signaling pathways, we studied the involvement of microtubules in STAT5B-mediated growth hormone signaling pathway in the highly differentiated and polarized WIF-B hepatic cell line. We showed that depolymerization of the microtubule network impaired STAT5B translocation to the nucleus upon growth hormone treatment. A significant amount of STAT5B binds to microtubules, while STAT5A and STAT3 are exclusively compartmentalized in the cytosol. Moreover, taxol-induced stabilization of microtubules released STAT5B from its binding, and we show that STAT5B binds specifically to the highly dynamic microtubules and is absent of the stable microtubule subpopulation. The specific involvement of dynamic microtubule subpopulation in growth hormone signaling pathway was confirmed by the inhibition of growth hormone-induced STAT5B nuclear translocation after stabilization of microtubules or specific disruption of highly dynamic microtubules. Upon growth hormone treatment, MT-bound STAT5B was rapidly released from microtubules by a dynein-dependent transport to the nucleus. Altogether, our findings indicate that the labile microtubule subpopulation specifically and dynamically organizes STAT5B-mediated growth hormone signaling in hepatic cells.Once bound to specific receptors, a large number of cytokines, growth factors, and hormones act through a sequence of steps allowing the rapid transport of information from the plasma membrane to subcellular targets. This information often results in the phosphorylation of transcription factors that subsequently migrate to the nucleus where they initiate specific gene transcription. How transcription factors are organized as molecular targets downstream of receptor activation and how they move rapidly through the cytoplasm from their activation site to the nucleus often remains unclear. The notion that microtubules (MTs) 1 might be involved in the cytoplasmic activation and/or trafficking of various transcription factors and protein kinases has emerged, as many signal transduction molecules, including transcription factors and protein kinases, have been shown to interact with MTs (1). For example, the glucocorticoid receptor was shown to colocalize with the MT network in mammalian cells (2, 3). The tumor suppressor protein p53 also uses MT tracks to migrate to the nucleus (4). Various protein kinases such as the MAP kinase kinase kinase MLK2 (5) or the MAP kinases ERK1 and ERK2 (6) were also shown to interact or to colocalize with MTs or with microtubule-associated proteins (7).In this study, we investigated the putative involvement of the MT network in GH signaling in the highly differentiated WIF-B hepatic cell line (8, 9...

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“…Mass spectrometry analysis of proteins captured by the eluted IgG when immobilized on magnetic beads identified 3 candidate proteins of 280kDa mass: MAP1B (270kDa), MAP1A (326kDa), and MAP2 (199kDa). 6,7 Confocal Microscopy Supports MAP1B as Primary Antigenic Target. Commercial IgG specific for MAP1B yielded a staining pattern on mouse tissues identical to that of patient IgG (Fig 2).…”

Section: Immunochemical Characterization Of the Autoantigen Pca-2 Igmentioning

confidence: 99%

Microtubule‐associated protein 1B: Novel paraneoplastic biomarker

Gadoth¹,

Kryzer²,

Fryer³

et al. 2017

Annals of Neurology

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Objective: To report the identification of microtubule-associated protein (MAP) 1B as the antigen of the previously described Purkinje cell cytoplasmic antibody type 2 (PCA-2) antibody, its frequency, and clinical, oncological, and serological associations. Methods: Archival serum or cerebrospinal fluid (CSF) specimens were available from 96 of 118 consecutive PCA-2-IgG-seropositive patients identified during 1993-2016. The autoantigen, defined in mouse brain lysate by Western blot and mass spectrometry, was confirmed by dual immunohistochemical staining using commercial antibodies. The major antigenic region was defined by Western blot using recombinant protein fragments. Results: IgG in 95 of 96 patients' serum or CSF (but in none of 98 healthy or disease control subjects' serum specimens) bound to recombinant MAP1B. A minority (17.5%) of patients' IgG also bound to MAP1A. PCA-2 was often accompanied by additional neural autoantibody markers of small-cell carcinoma, including collapsin responsemediated protein 5 (CRMP5) IgG (26%) or antineuronal nuclear antibody type 1 (ANNA-1) IgG (also known as antiHu; 13%). Neurological manifestations in 95 patients were (in decreasing frequency): peripheral neuropathy, 53%; cerebellar ataxia, dysmetria, or dysarthria, 38%; and encephalopathy, 27%. Cancer (majority small-cell lung carcinoma [SCLC]) was detected in 66 of 84 evaluated patients (79%). The MAP1B (PCA-2) autoantibody detection rate, among approximately 70,000 patients undergoing service neural autoantibody evaluation in 2015, was 0.024%, equaling amphiphysin IgG (0.026%) and more common than ANNA-2 (also known as anti-Ri; 0.016%) and PCA-Tr (also known as delta/notch-like epidermal growth factor-related receptor [DNER]; 0.006%). Interpretation: MAP1B, the PCA-2 autoantigen, represents a novel target in paraneoplastic neurological disorders and has high predictive value for SCLC. Its relatively high prevalence, compared with other recognized paraneoplastic neural autoantibodies, justifies its testing in comprehensive paraneoplastic neural autoantibody evaluation. ANN NEUROL 2017;81:266-277 I n 2000, Vernino and Lennon 1 reported 10 patients with neurological autoimmunity, 9 of whom had imaging or histopathologic evidence of lung cancer (8 biopsyproven small-cell lung carcinoma [SCLC]). Their serum IgG bound to a protein of 280kDa mass in both rodent brain and a SCLC line and yielded a characteristic staining pattern on rodent neural tissues. The autoantibody was named Purkinje cell cytoplasmic antibody type 2 (PCA-2), to distinguish it from a biomarker of ovarian and breast cancer-related cerebellar degeneration, PCA-1 (also known as anti-Yo). 2 The neurological associations initially reported for PCA-2 were mixed, of subacute onset and predominantly central (brainstem and limbic encephalitis, cerebellar ataxia), but some patients had peripheral manifestations (Lambert-Eaton myasthenic syndrome [LEMS] or autonomic or motor neuropathy). 1 Our study extends the immunochemical characteristization of PCA-2 IgG an...

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Regulated Association of Microtubule-associated Protein 2 (MAP2) with Src and Grb2: Evidence for MAP2 as a Scaffolding Protein

Cited by 79 publications

References 72 publications

NMDA Receptor Activation Suppresses Microtubule Growth and Spine Entry

NMDA Receptor Activation Suppresses Microtubule Growth and Spine Entry

STAT5B-mediated Growth Hormone Signaling Is Organized by Highly Dynamic Microtubules in Hepatic Cells

Microtubule‐associated protein 1B: Novel paraneoplastic biomarker

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