A novel direct interaction of endoplasmic reticulum with microtubules

Klopfenstein, Dieter R.; Kappeler, Felix; Hauri, Hans‐Peter

doi:10.1093/emboj/17.21.6168

Cited by 182 publications

(228 citation statements)

References 58 publications

(67 reference statements)

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“…7). In HeLa cells, one band of 63 kDa was revealed with both the monoclonal and polyclonal antibody directed against p63 as reported previously (37,38). However, when immunoprecipitation was performed on HeLa cells expressing fulllength tau or the GFP alone, no p63 was detected in either tau or GFP immunoprecipitate.…”

Section: Fig 5 the Interaction Of Map2c And P63 In An Overlay Assaysupporting

confidence: 77%

“…Here we report a novel association of MAP2 with RER membranes using subcellular fractionation, electron microscopy immunocytochemistry, and electron microscopy in an in vitro reconstitution assay. Moreover, we showed that this association involves the interaction of the MAP2 projection domain with a 63-kDa nonglycosylated type II integral RER membrane protein, termed p63, that was found to mediate the interaction between RER membranes and microtubules in a previous study (37)(38)(39). Taken together, our results suggest that the interaction between MAP2 and p63 might contribute to the preferential distribution of RER membranes in the dendritic processes.…”

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confidence: 69%

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Interaction of Microtubule-associated Protein-2 and p63

Farah

Liazoghli

Perreault

et al. 2005

Journal of Biological Chemistry

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Neurons are polarized cells presenting two distinct compartments, dendrites and an axon. Dendrites can be distinguished from the axon by the presence of rough endoplasmic reticulum (RER). The mechanism by which the structure and distribution of the RER is maintained in these cells is poorly understood. In the present study, we investigated the role of the dendritic microtubuleassociated protein-2 (MAP2) in the RER membrane positioning by comparing their distribution in brain subcellular fractions and in primary hippocampal cells and by examining the MAP2-microtubule interaction with RER membranes in vitro. Subcellular fractionation of rat brain revealed a high MAP2 content in a subfraction enriched with the endoplasmic reticulum markers ribophorin and p63. Electron microscope morphometry confirmed the enrichment of this subfraction with RER membranes. In cultured hippocampal neurons, MAP2 and p63 were found to concomitantly compartmentalize to the dendritic processes during neuronal differentiation. Protein blot overlays using purified MAP2c protein revealed its interaction with p63, and immunoprecipitation experiments performed in HeLa cells showed that this interaction involves the projection domain of MAP2. In an in vitro reconstitution assay, MAP2-containing microtubules were observed to bind to RER membranes in contrast to microtubules containing tau, the axonal MAP. This binding of MAP2c microtubules was reduced when an anti-p63 antibody was added to the assay. The present results suggest that MAP2 is involved in the association of RER membranes with microtubules and thereby could participate in the differential distribution of RER membranes within a neuron.Neurons are polarized cells that present two distinct compartments, dendrites and an axon. These compartments can be distinguished by their morphology; dendrites are multiple and taper, whereas the axon is unique and its diameter is uniform (1-4). Dendrites and axon also differ by their membranous organelle composition; RER 1 is found in the somato-dendritic compartment but not in the axon, and the number of free ribosomes is a lot higher in dendrites than in the axon (1, 2, 5). The cytoskeletal elements are also distinctly distributed in these neuronal compartments; the number of microtubules is higher in dendrites than in the axon, whereas the opposite is noted for neurofilaments (1, 2, 6).Microtubules are involved in the establishment of cell polarity. Notably, the microtubules of dendrites and axon contain different microtubule-associated proteins (MAPs); the microtubule-associated protein-2 (MAP2) is found in dendrites, whereas tau is present only in the axon (6 -8). The contribution of these MAPs to the establishment of neuronal polarity has been well documented. Tau contributes to the axonal differentiation in primary neuronal cultures, whereas MAP2 is involved in the differentiation of minor neurites, the neuronal processes that become dendrites, and in the maintenance of dendrites in adult neurons (9 -14). Despite the fact that MAP2 and tau are...

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Section: Fig 5 the Interaction Of Map2c And P63 In An Overlay Assaysupporting

confidence: 77%

supporting

confidence: 69%

Interaction of Microtubule-associated Protein-2 and p63

Farah

Liazoghli

Perreault

et al. 2005

Journal of Biological Chemistry

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“…7 and 8), which was very reminiscent of the ER rearrangement in COS-7 cells induced by overexpression of the cytoskeleton-binding membrane protein CLIMP-63 (58,59). In the case of CLIMP-63, this ER rearrangement is a direct consequence of the interactions between the cytoplasmic domain of CLIMP-63 with microtubules along the altered ER membranes (58). The reason why ADAM12 was able to induce a similar ER rearrangement is not clear, and the possibility that ADAM12 may interact with microtubules needs to be explored.…”

Section: Discussionmentioning

confidence: 99%

Intracellular Processing of Metalloprotease Disintegrin ADAM12

Cao

Kang

Zhao

et al. 2002

Journal of Biological Chemistry

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ADAM12 has been implicated in cell-cell interactions in myogenesis and cancer, but the structure of the mature form of ADAM12 is not known, and its localization on the cell surface has been questioned. In this report, we show that full-length ADAM12 is N-glycosylated in the endoplasmic reticulum (ER) and proteolytically processed in the trans-Golgi network to an ϳ90-kDa form. The ϳ90-kDa form, which lacks the prodomain, was the predominant form present at the cell surface. Replacement of Leu 73 in the putative ␣-helical region in the prodomain with proline resulted in retention of ADAM12 in the ER and a complete lack of its processing. However, deletion of the entire pro-and metalloprotease domains did not affect the processing and trafficking of ADAM12. In contrast, replacement of the cytoplasmic domain of ADAM12 with that of ADAM9 or adding a c-Myc tag at the C terminus led to a significant increase in transport of the protein to the cell surface. These results suggest that the cytoplasmic domain of ADAM12 plays an important role in regulating ADAM12 exit from the ER. We conclude that properly folded mouse ADAM12, after passing a rate-limiting step of exit from the ER, is processed in the secretory pathway and reaches the cell surface, where it can mediate adhesionmediated signaling.ADAMs, a family of proteins containing a disintegrin and metalloprotease domain, play important roles in many biological processes involving cell-surface proteolysis and cell-cell or cell-matrix interactions (1-3). ADAMs have been implicated in many vital functions during development (4 -7) and in the pathogenesis of cancer (8 -10), rheumatoid arthritis (11), Alzheimer's disease (12), and inflammatory responses (9). With an exception of the ADAMTS subfamily (ADAMs with thrombospondin motifs) and alternative splice variants of several family members, ADAMs are type I transmembrane proteins expressed in all animal organisms from worm to human. A typical ADAM protein contains an N-terminal secretion signal and pro-, metalloprotease, disintegrin-like, cysteine-rich, epidermal growth factor-like, transmembrane, and cytoplasmic domains.The metalloprotease domains of many, but not all, ADAMs contain a consensus sequence (HEXXHXXGXXH) for the active site of zinc-dependent metalloproteases (13). These ADAMs are predicted to be active proteases involved in shedding of the ectodomains of membrane proteins, which is critical for cellsurface remodeling, regulating growth factor availability, and modulating the capacity of cells to respond to extracellular stimuli (14, 15). At least six members of the ADAM family have been demonstrated to have proteolytic activity. ADAM17 (tumor necrosis factor-␣-converting enzyme) releases soluble tumor necrosis factor-␣ from its membrane precursor (16,17). It also cleaves the tumor necrosis factor-␣ receptor, transforming growth factor-␣, and L-selectin (6); interleukin-1 receptor type II (18); amyloid precursor protein (12); ErbB4/HER4, a member of the epidermal growth factor receptor family (19); and Notch (...

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“…For example, in mammals, CLIMP63 (cytoskeletal linking membrane protein p63) is required to interact with microtubules to stabilize the cortical ER network (see review in Vedrenne and Hauri [2006] and references therein; Klopfenstein et al, 1998). Growth of tubules in animal systems is also dependent on integral ER membrane proteins (e.g., stromal interaction molecule 1) that bind the plus end of growing microtubules (Grigoriev et al, 2008).…”

Section: Three-way Junction and Anchor Sites Are Stabilization Factormentioning

confidence: 99%

Movement and Remodeling of the Endoplasmic Reticulum in Nondividing Cells of Tobacco Leaves

et al. 2009

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Using a novel analytical tool, this study investigates the relative roles of actin, microtubules, myosin, and Golgi bodies on form and movement of the endoplasmic reticulum (ER) in tobacco (Nicotiana tabacum) leaf epidermal cells. Expression of a subset of truncated class XI myosins, which interfere with the activity of native class XI myosins, and drug-induced actin depolymerization produce a more persistent network of ER tubules and larger persistent cisternae. The treatments differentially affect two persistent size classes of cortical ER cisternae, those >0.3 mm 2 and those smaller, called punctae. The punctae are not Golgi, and ER remodeling occurs in the absence of Golgi bodies. The treatments diminish the mobile fraction of ER membrane proteins but not the diffusive flow of mobile membrane proteins. The results support a model whereby ER network remodeling is coupled to the directionality but not the magnitude of membrane surface flow, and the punctae are network nodes that act as foci of actin polymerization, regulating network remodeling through exploratory tubule growth and myosin-mediated shrinkage.

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A novel direct interaction of endoplasmic reticulum with microtubules

Cited by 182 publications

References 58 publications

Interaction of Microtubule-associated Protein-2 and p63

Interaction of Microtubule-associated Protein-2 and p63

Intracellular Processing of Metalloprotease Disintegrin ADAM12

Movement and Remodeling of the Endoplasmic Reticulum in Nondividing Cells of Tobacco Leaves

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