Association of stomatin with lipid-protein complexes in the plasma membrane and the endocytic compartment

Snyers, Luc; Umlauf, Ellen; Prohaska, Rainer

doi:10.1016/s0171-9335(99)80031-4

Cited by 94 publications

(121 citation statements)

References 34 publications

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“…The results with Triton agreed with earlier observations (6,11,(20)(21)(22). Regarding Lubrol WX, calnexin had previously been found to be partly insoluble (15), consistent with our results.…”

Section: Protein Analysis Of Drms Prepared With Different Detergentssupporting

confidence: 93%

Resistance of cell membranes to different detergents

Schuck

Honsho

Ekroos

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

602

557

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Partial resistance of cell membranes to solubilization with mild detergents and the analysis of isolated detergent-resistant membranes (DRMs) have been used operationally to define membrane domains. Given the multitude of detergents used for this purpose, we sought to investigate whether extraction with different detergents might reflect the same underlying principle of domain formation. We therefore compared the protein and lipid content of DRMs prepared with a variety of detergents from two cell lines. We found that the detergents differ considerably in their ability to selectively solubilize membrane proteins and to enrich sphingolipids and cholesterol over glycerophospholipids as well as saturated over unsaturated phosphatidylcholine. In addition, we observed cell type-dependent variations of the molecular characteristics of DRMs and the effectiveness of particular detergents. These results make it unlikely that different detergents reflect the same aspects of membrane organization and underscore both the structural complexity of cell membranes and the need for more sophisticated analytical tools to understand their architecture.

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Section: Protein Analysis Of Drms Prepared With Different Detergentssupporting

confidence: 93%

Resistance of cell membranes to different detergents

Schuck

Honsho

Ekroos

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

602

557

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“…Podocin is a recently identified protein of the raft-associated stomatin family 41 whose gene NPHS2 is mutated in families with autosomal-recessive steroidresistant nephrotic syndrome. 42 Interestingly, podocin localizes to the slit diaphragm and associates with the nephrin-containing raft (K Schwarz, M Simons, J Reiser, W Kriz, LB Holzman, AS Shaw, and P Mundel, submitted for publication). It will be interesting to see what other molecules, eg, kinases, can be found in this specialized microdomain and how their function and organization is affected in different pathological situations.…”

Section: Discussionmentioning

confidence: 99%

Involvement of Lipid Rafts in Nephrin Phosphorylation and Organization of the Glomerular Slit Diaphragm

Simons

Schwarz

Kriz

et al. 2001

The American Journal of Pathology

145

126

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NPHS1 has recently been identified as the gene whose mutations cause congenital nephrotic syndrome of the Finnish type. The respective gene product nephrin is a transmembrane protein expressed in glomerular podocytes and primarily localized to the glomerular slit diaphragm. This interpodocyte junction functions in the glomerular filtration by restricting the passage of plasma proteins into the urinary space in a size-selective manner. The functional role of nephrin in this filtration process is so far not very well understood. In this study, we show that nephrin associates in an oligomerized form with signaling microdomains, also known as lipid rafts, and that these localize to the slit diaphragm. We also show that the nephrin-containing rafts can be immunoisolated with the 27A antibody recognizing a podocyte-specific 9-Oacetylated GD3 ganglioside. In a previous study it has been shown that the in vivo injection of this antibody leads to morphological changes of the filtration slits resembling foot process effacement. Here, we report that, in this model of foot process effacement, nephrin dislocates to the apical pole of the narrowed filtration slits and also that it is tyrosine phosphorylated. We suggest that lipid rafts are important in the spatial organization of the glomerular slit diaphragm under physiological and pathological conditions. One of the main functions of the kidney is formation of the primary urine in the glomerulus by plasma ultrafiltration. The structural correlate of ultrafiltration is the glomerular capillary wall with its distinctly layered filtration barrier. It consists of the fenestrated vascular endothelium, the glomerular basement membrane, and a layer of morphologically highly specialized epithelial cells, podocytes.Podocytes form a tight network of multiple interdigitating cellular extensions, called foot processes, which are bridged by so-called "slit diaphragms." 1 The filtration barrier is freely permeable for water, small solutes, and ions but does not allow passage for proteins larger than albumin and other large molecules. The charge selectivity in this process has been attributed to the glomerular basement membrane whereas the slit diaphragm supposedly plays a major role in the size selectivity. 2,3 The importance of the filtration barrier is reflected by a number of human diseases in which the filtration barrier function is disrupted resulting in the loss of plasma proteins into the urine. Patients with persistent proteinuria ultimately develop a nephrotic syndrome with a variety of symptoms including edema, hypoalbuminemia, and hyperlipidemia. 4

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“…Proteins of the SPFH superfamily have been linked to the organization of membrane microdomains (26)(27)(28)(29)(30)(31). Based on this assumption, and because SLP-2 is mostly a mitochondrial protein localized in the intermembrane space (32, 33), we examined if SLP-2 deficiency would alter mitochondrial membrane compartmentalization.…”

Section: Slp-2 Deficiency Is Associated With Abnormal CL Compartmentamentioning

confidence: 99%

Stomatin-like Protein 2 Deficiency in T Cells Is Associated with Altered Mitochondrial Respiration and Defective CD4+ T Cell Responses

Christie

Mitsopoulos

Blagih

et al. 2012

The Journal of Immunology

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Stomatin-like protein 2 (SLP-2) is a mostly mitochondrial protein that regulates mitochondrial biogenesis and function and modulates T cell activation. To determine the mechanism of action of SLP-2, we generated T cell-specific SLP-2–deficient mice. These mice had normal numbers of thymocytes and T cells in the periphery. However, conventional SLP-2–deficient T cells had a posttranscriptional defect in IL-2 production in response to TCR ligation, and this translated into reduced CD4+ T cell responses. SLP-2 deficiency was associated with impaired cardiolipin compartmentalization in mitochondrial membranes, decreased levels of the NADH dehydrogenase (ubiquinone) iron-sulfur protein 3, NADH dehydrogenase (ubiquinone) 1β subcomplex subunit 8, and NADH dehydrogenase (ubiquinone) 1α subcomplex subunit 9 of respiratory complex I, and decreased activity of this complex as well as of complex II plus III of the respiratory chain. In addition, SLP-2–deficient T cells showed a significant increase in uncoupled mitochondrial respiration and a greater reliance on glycolysis. Based on these results, we propose that SLP-2 organizes the mitochondrial membrane compartmentalization of cardiolipin, which is required for optimal assembly and function of respiratory chain complexes. This function, in T cells, helps to ensure proper metabolic response during activation.

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Association of stomatin with lipid-protein complexes in the plasma membrane and the endocytic compartment

Cited by 94 publications

References 34 publications

Resistance of cell membranes to different detergents

Resistance of cell membranes to different detergents

Involvement of Lipid Rafts in Nephrin Phosphorylation and Organization of the Glomerular Slit Diaphragm

Stomatin-like Protein 2 Deficiency in T Cells Is Associated with Altered Mitochondrial Respiration and Defective CD4+ T Cell Responses

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