Plectin scaffolds recruit energy-controlling AMP-activated protein kinase (AMPK) in differentiated myofibres

Gregor, Martin; Zeöld, Anikó; Oehler, Susanne; Marobela, Kerstin Andrä; Fuchs, Peter; Weigel, Günter; Dg, Hardie; Wiche, Gerhard

doi:10.1242/jcs.02891

Cited by 60 publications

(55 citation statements)

References 65 publications

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“…Immunofluorescence colocalization images indicate that plectin and DG co-reside in perinuclear focal adhesion sites. Moreover, immunoprecipitation data indicate that plectin serves as a scaffold for AMPK, a finding consistent with evidence that plectin binds to AMPK in myocytes to regulate energy homeostasis (45). In addition, our data demonstrate that DG has a dual role by acting not only as the mechanical receptor to receive signals from the stretched ECM but also as a scaffold to recruit ERK1/2.…”

Section: Discussionsupporting

confidence: 89%

“…Plectin Knockdown Has No Effect on the Cytoskeletal Networks of AECs-Because plectin interacts with DG in muscle cells and also has the ability to bind AMPK in these cells (22,45), we hypothesized that plectin might mediate DG-dependent pathway bifurcation in AECs. To test this hypothesis, we first generated adenoviruses encoding plectin-specific shRNA.…”

Section: Is the Cytoskeleton Involved In Stretch Activation Of Signalmentioning

confidence: 99%

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A Dystroglycan/Plectin Scaffold Mediates Mechanical Pathway Bifurcation in Lung Epithelial Cells

Takawira¹,

Budinger

Hopkinson³

et al. 2011

Journal of Biological Chemistry

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In alveolar epithelial cells (AECs), the membrane-anchored proteoglycan dystroglycan (DG) is a mechanoreceptor that transmits mechanical stretch forces to activate independently the ERK1/2 and the adenosine 5-monophosphate-activated protein kinase (AMPK) signaling cascades in a process called pathway bifurcation. We tested the hypothesis that the cytoskeleton cross-linker plectin, known to bind both DG and AMPK in muscle cells, acts as a scaffold to regulate DG-mediated mechanical stimulation and pathway bifurcation. We demonstrate that plectin and DG form a complex in AECs and that this complex interacts with ERK1/2 and AMPK. Plectin knockdown reduces DG interaction with AMPK but not with ERK1/2. Despite this, mechanoactivation of both signaling pathways is significantly attenuated in AECs deficient in plectin. Thus, DG has the dual role of mechanical receptor and scaffold for ERK1/2, whereas plectin acts as a scaffold for AMPK signaling but is also required for DG-mediated ERK1/2 activation. We conclude that the DG-plectin complex plays a central role in transmitting mechanical stress from the extracellular matrix to the cytoplasm.In the lung, alveolar epithelial cells (AECs) 3 not only mediate the exchange of gases between the circulation system of the host and its external environment but are also highly responsive to a number of mechanical forces (1). These forces include deformation and strain that occur during lung expansion and relaxation from breathing movements, and shear stress during the distension of the airway walls and blood vessels from bulk air and blood flow (2). Over the past few years, there has been increasing interest in identifying molecules that "sense" physical forces on the cell surface and in defining the signaling pathways activated by mechanical stimulation (1, 3-6). Stretch-activated ion channels, integrins, cell-cell adhesion molecules, cytoskeleton elements, and the extracellular matrix (ECM) have all been implicated in transducing mechanical signals in a manner that is detectable as chemical signals (e.g. protein phosphorylation) in the cytoplasm of the stimulated cell (1, 7).We are interested in investigating the molecular underpinnings of cellular responses to physical force in rat AECs. In particular, we have previously tested the hypothesis that matrix molecules secreted by cultured AECs and transmembrane matrix receptors on the substratum surface of these cells are crucial molecular links in the process of "converting" a mechanical stimulus in the form of cyclic stretching into a cytoplasmic signal (8). Specifically, in prior studies we demonstrated that rat AECs assemble an ECM rich in fibers composed of the ␣3, ␤1, and ␥1 subunits of laminin (laminin-311), complexed with perlecan and nidogen (8). This complex transmits mechanosignals in the form of stretch, via the matrix receptor dystroglycan (DG), to activate ERK1/2 (8). Moreover, we have also shown that DG is required for stretch-induced activation of the adenosine 5Ј-monophosphate-activated protein kinase (AMPK) sign...

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Section: Discussionsupporting

confidence: 89%

Section: Is the Cytoskeleton Involved In Stretch Activation Of Signalmentioning

confidence: 99%

A Dystroglycan/Plectin Scaffold Mediates Mechanical Pathway Bifurcation in Lung Epithelial Cells

Takawira¹,

Budinger

Hopkinson³

et al. 2011

Journal of Biological Chemistry

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“…The importance of the mitochondria-cytoskeleton docking makes slow oxidative fibers more sensitive to the lack of plectin than fast glycolytic fibers (428). Accordingly, plectin is more abundantly expressed in mitochondria-rich slow oxidative type I, compared with glycolytic type II muscle fibers (293). ␥-Actin filaments are present both around the myofibrils at the Zdisc level and in subsarcolemmal location likely contributing to link myofibrillar networks to the membrane systems.…”

Section: Fiber Types In Mammalian Skeletal Musclesmentioning

confidence: 99%

Fiber Types in Mammalian Skeletal Muscles

Schiaffino

Reggiani

2011

Physiological Reviews

2,233

2,465

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Mammalian skeletal muscle comprises different fiber types, whose identity is first established during embryonic development by intrinsic myogenic control mechanisms and is later modulated by neural and hormonal factors. The relative proportion of the different fiber types varies strikingly between species, and in humans shows significant variability between individuals. Myosin heavy chain isoforms, whose complete inventory and expression pattern are now available, provide a useful marker for fiber types, both for the four major forms present in trunk and limb muscles and the minor forms present in head and neck muscles. However, muscle fiber diversity involves all functional muscle cell compartments, including membrane excitation, excitation-contraction coupling, contractile machinery, cytoskeleton scaffold, and energy supply systems. Variations within each compartment are limited by the need of matching fiber type properties between different compartments. Nerve activity is a major control mechanism of the fiber type profile, and multiple signaling pathways are implicated in activity-dependent changes of muscle fibers. The characterization of these pathways is raising increasing interest in clinical medicine, given the potentially beneficial effects of muscle fiber type switching in the prevention and treatment of metabolic diseases.

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“…For instance, plectin was shown to bind and sequester receptor 154 for activated C kinase, a protein kinase C binding partner (Ron et al, 1994), to the cytoskeleton, thereby affecting the protein kinase C signaling pathway (Osmanagic-Myers and Wiche, 2004). Plectin also interacts with other proteins such as desmoplakin (Eger et al, 1997), fodrin (Herrmann and Wiche, 1987;Eger et al, 1997), ␤4 integrin (Rezniczek et al, 1998), spectrin (Herrmann and Wiche, 1987), Fer kinase (Lunter and Wiche, 2002), AMP-activated protein kinase (Gregor et al, 2006), lamin B (Foisner et al, 1991), nesprin-3 [an outer nuclear envelope protein (Wilhelmsen et al, 2005;Ketema et al, 2007)], and seven in absentia homolog [Siah, an ubiquitin E3 ligase (House et al, 2003)]. The interaction between plectin and Siah may suggest that plectin facilitates the degradation of cytoplasmic proteins such as ␤-catenin (Liu et al, 2001;Matsuzawa and Reed, 2001;Park et al, 2006b).…”

Section: Anchoring Junctions and Male Contraceptionmentioning

confidence: 99%