Neuronal Expression of the ERM-like Protein MIR in Rat Brain and Its Localization to Human Chromosome 6

Olsson, Per-Anders; Bornhäuser, Beat; Korhonen, Laura; Lindholm, Dan

doi:10.1006/bbrc.2000.4028

Cited by 18 publications

(9 citation statements)

References 15 publications

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“…This antiserum recognized MSAP in Western blots. For immunocytochemistry, primary hippocampal neurons and COS7 cells were cultured, fixed, and stained as described (19). Anti-MSAP antibody (diluted 1:200) or anti-MIR antibody (1:200) was added and incubated overnight at 4°C.…”

Section: Methodsmentioning

confidence: 99%

“…MSAP and MIR Co-localize in Cells-Previous studies have shown the localization of MIR in the cytosol and at membranous structures in overexpressing cells (15,19). To study the subcellular localization of MSAP, COS7 cells and primary hippocampal neurons were cultured and stained with anti-MIRand anti-MSAP-specific antibodies.…”

Section: Msap Belongs To the Family Of Saposin-like Proteins And Is Ementioning

confidence: 99%

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MSAP Is a Novel MIR-interacting Protein That Enhances Neurite Outgrowth and Increases Myosin Regulatory Light Chain

Bornhäuser¹,

Olsson

Lindholm

2003

Journal of Biological Chemistry

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Interactions between the cell membrane and the cytoskeleton play a major role in different aspects of cell differentiation, such as cell motility, cell division, and establishment of cellular architecture. Of particular importance in this context is the association of cortical actin with the cell membrane. The ERM 1 proteins, ezrin, radixin, and moesin, are members of the large 4.1 protein family and are involved in membrane-cytoskeleton interactions. They link the actin cytoskeleton to membranebound proteins located at different membrane sites, i.e. microvilli, membrane ruffles, and cell-cell contacts (1-3). This is accomplished by binding of the C-terminal part of the ERM proteins to actin and of the N-terminal FERM domain to specific membrane proteins (4). FERM domains have been found in many different proteins and are thought to be modules for protein-protein and protein-membrane interactions (5). The ERM proteins are involved in cell adhesion and signal transduction events through phosphorylation (6, 7) and interaction with phosphoinositides (8). The ERM proteins play an important role in the activation of Rho family proteins and can interact both downstream (9) and upstream (10) of Rho.In addition, the ERM proteins are involved in membrane dynamics (11). When ezrin, radixin, and moesin were simultaneously inactivated by antisense treatment in epithelial cells, cell-cell and cell-substratum adhesion was altered (12). Double suppression of radixin and moesin, but not ezrin and radixin or moesin, alters growth cone motility, inhibiting neurite extension (13). In contrast, overexpression of ezrin in insect cells leads to enhanced cell adhesion (14). The mechanisms behind these effects are, however, not well understood, but ERM proteins are known to interact with various proteins such as CD44 and ICAM-1, -2, and -3, which helps in establishing membrane specializations (for review, see Ref. 7). The identification and characterization of further binding partners for ERM proteins can give new insights into the function of these proteins.We have recently identified a novel ERM family protein, MIR, which has an ERM domain at the N terminus and lacks actin binding, instead possessing a RING domain in the Cterminal region (15). Overexpression of MIR abrogated neurite outgrowth in PC12 cells, an effect that may be brought about by its interaction with the myosin regulatory light chain (MRLC). We describe here a novel protein interacting with MIR, called MIR-interacting saposin-like protein (MSAP), which stimulates neurite outgrowth. Sequence comparisons showed that MSAP contains a saposin domain, which is found, among others, in the sphingolipid activator proteins, the saposins (16), and in some saposin-like proteins with a similar structure (17). The effects of MSAP on neurite outgrowth were reduced by MIR. MIR was shown to induce a decrease in the levels of MRLC, which could be blocked by overexpression of MSAP or by inhibition of proteasome activity. Evidence was obtained that the decrease in MRLC levels by MIR invo...

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Section: Methodsmentioning

confidence: 99%

Section: Msap Belongs To the Family Of Saposin-like Proteins And Is Ementioning

confidence: 99%

MSAP Is a Novel MIR-interacting Protein That Enhances Neurite Outgrowth and Increases Myosin Regulatory Light Chain

Bornhäuser¹,

Olsson

Lindholm

2003

Journal of Biological Chemistry

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“…Functional data revealed that overexpression of Mylip inhibited nerve growth factor-driven neurite outgrowth in neuronal PC12 cells that was associated with the downregulation of MRLC by Mylip-induced protein ubiquitination [18,20]. In line with this, Mylip is expressed in neurons in hippocampus and in cerebellum during brain development [21]. Mylip is also abundantly expressed in almost all human tissues, suggesting additional functions and targets for this protein.…”

Section: Nuclear Receptor Lxr Induces Mylip/idolmentioning

confidence: 55%

Mylip makes an Idol turn into regulation of LDL receptor

Lindholm

Bornhäuser

Korhonen

2009

Cell. Mol. Life Sci.

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High blood low-density-lipoprotein (LDL) cholesterol is a serious health problem among an increased number of patients in the Western world. Statins and other cholesterol lowering drugs have proven to be beneficial as therapy but are not optimal and show adverse effects in some patients. The LDL receptor is a crucial determinant of cholesterol metabolism in the body and amenable for drug interventions. Novel insights into the physiology of this receptor come from studies on the ubiquitination and degradation of LDL receptor by the ubiquitin ligase Mylip/Idol that is induced in cells by the nuclear receptor, LXR. This may open up new possibilities in the future to influence LDL receptor levels and cholesterol metabolism pharmacologically in various diseases.

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“…Over expression of Mylip can inhibit nerve growth factor-stimulated neurite outgrowth in PC12 neuronal cells, presumably due to the ubiquitination and degradation of myosin regulatory light chain (Bornhauser and Lindholm, 2005). In the rat, Mylip expression is localized especially to neurons in the hippocampus and cerebellum, both during development and in adult brain (Olsson et al, 2000). Mylip expression can also be detected in many other tissues, suggesting additional functions and targets for this protein.…”

Section: The Role Of Idol In Regulating Ldlrmentioning

confidence: 99%

Novel Regulators of Low-Density Lipoprotein Receptor and Circulating LDL-C for the Prevention and Treatment of Coronary Artery Disease

Cao¹,

Konrad²,

Kowala³

et al. 2012

Coronary Artery Disease - New Insights and Novel Approaches

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Neuronal Expression of the ERM-like Protein MIR in Rat Brain and Its Localization to Human Chromosome 6

Cited by 18 publications

References 15 publications

MSAP Is a Novel MIR-interacting Protein That Enhances Neurite Outgrowth and Increases Myosin Regulatory Light Chain

MSAP Is a Novel MIR-interacting Protein That Enhances Neurite Outgrowth and Increases Myosin Regulatory Light Chain

Mylip makes an Idol turn into regulation of LDL receptor

Novel Regulators of Low-Density Lipoprotein Receptor and Circulating LDL-C for the Prevention and Treatment of Coronary Artery Disease

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