Location of Repository

Functional characterisation of the lipid raft protein stomatin

By Dorothy Kate Wilkinson

Abstract

The function of the integral membrane protein stomatin is as yet poorly understood. Stomatin is deficient from the erythrocyte membrane of patients suffering with Overhydrated\ud Hereditary Stomatocytosis (OHSt). Patient erythrocytes have altered morphology and are known as stomatocytes. It is believed that stomatin is mistrafficked in the developing stomatocyte. These patients suffer grossly abnormal\ud cation fluxes in the stomatocyte membrane which causes increased osmotic fragility of the cell and results in haemolytic anaemia. This study set out to characterise\ud further stomatin and to investigate its role in the cell. The membranes and lipid rafts of stomatocytes were found to have reduced actin levels as compared to erythrocytes, suggesting that stomatin may function as a structural protein linking the cytoskeleton to the membrane. Overexpression of stomatin in nucleated cells\ud caused enhanced actin association with cell membranes and lipid rafts, further confirming the findings from stomatocytes. Calcium-induced vesiculation was found\ud to be significantly enhanced from the stomatocyte as compared to the erythrocyte, with defective partitioning of the flotillin proteins into the vesicles. This suggests that\ud stomatin may function as a negative regulator in this vesiculation, possibly due to its interaction with actin and that the flotillins may substitute for stomatin in this process within the stomatocyte.\ud \ud Mutating the principle cysteine residue for palmitoylation within stomatin caused the protein to show less affinity for the membrane and lipid rafts but an increased affinity\ud for the nucleus. This suggests that palmitoylation of stomatin affects the affinity of stomatin for the membrane and that this modification may be involved in regulating\ud the shuttling of stomatin between the plasma membrane and the nucleus.\ud \ud Prokaryotic stomatin exists in an operon with a serine protease, suggesting a functional link between the two. Using a reporter gene construct approach the\ud potential for mammalian stomatin to be proteolytically processed was investigated. Stomatin was found to be proteolytically processed in the membrane by a serine\ud protease with the subsequent release of a C-terminal fragment

Publisher: Faculty of Biological Sciences (Leeds)
Year: 2005
OAI identifier: oai:etheses.whiterose.ac.uk:448

Suggested articles

Preview

Citations

  1. (2004). A family showing recessively inherited multisystem pathology with aberrant splicing of the erythrocyte Band 7.2b ('stomatin') gene. " doi
  2. (2002). A role for lipid shells in targeting proteins to caveolae, rafts, and other lipid domains. " doi
  3. (2004). A stomatin and a degenerin interact in lipid rafts of the nervous system of Caenorhabditis elegans. " doi
  4. (1995). A stomatin-like protein necessary for mechanosensation in doi
  5. (2001). A transcriptionally [correction of transcriptively] active complex of APP with Fe65 and histone acetyltra nsfe rase Tip60. " doi
  6. (1993). Absence of lipid gel-phase domains in seven mammalian cell lines and in four primary cell types. " doi
  7. (2005). Angelova doi
  8. (1999). Association of stomatin (band 7.2b) with Glutl glucose transporter. " doi
  9. (1999). Association of stomatin with lipidprotein complexes in the plasma membrane and the endocytic compartment. " doi
  10. (2004). Association of stornatin with lipid bodies. "
  11. (2003). ATP-dependent vesiculation in red cell membranes from different hereditary stomatocytosis variants. " doi
  12. (2005). Bacterial invasion via lipid rafts. " doi
  13. (1995). Both sphingolipids and cholesterol participate in the detergent insolubility of alkaline phosphatase, a glycosylphosphatidylinositol-anchored protein, in mammalian membranes. " doi
  14. (2002). Ca(++)-dependent vesicle release from erythrocytes involves stomatin-specific lipid rafts, synexin (annexin VII), and sorcin. " doi
  15. (2002). Calpain 11 colocalizes with detergent-insoluble rafts on human and Jurkat T-cells. " doi
  16. (1994). Caveolin moves from caveolae to the Golgi apparatus in response to cholesterol oxidation. " doi
  17. (2001). Caveolin, cholesterol, and lipid droplets? " doi
  18. (2005). Cell biology. Ras on the roundabout. " doi
  19. (2002). Cell-surface expression of the channel activating protease xCAP-1 is required for activation of ENaC in the Xenopus oocyte. "
  20. (1993). Cells lacking glycan phosphatidylinositol-linked proteins have impaired ability to vesiculate. "
  21. (2001). Characterization of cholesterol-sphingomyelin domains and their dynamics in bilayer membranes. " doi
  22. Cholesterol and sphingolipid enhance the Triton X-100 insolubility of g lycosylphos phatidyl i nositol-ancho red proteins by promoting the formation of detergent-insoluble ordered membrane domains. " doi
  23. (1996). Cholesterol at different bilayer concentrations can promote or antagonize lateral segregation of phospholipids of differing acyl chain length. " doi
  24. (1990). Cholesterol controls the clustering of the glycophospholipid-anchored membrane receptor for 5-methyltetrahyd rofo late. "
  25. (1991). Cloning and nucleotide sequence of cDNA encoding human erythrocyte band 7 integral membrane protein. " doi
  26. (2005). Cold-induced coalescence of T-cell plasma membrane microdomains activates signalling pathways. " doi
  27. (1997). Colocalization of stomatin (band 7.2b) and actin microfilaments in UAC epithelial cells. "
  28. (1999). Cysteine 29 is the major palmitoylation site on stomatin. ". doi
  29. (1999). Deciphering the nuclear import pathway for the cytoskeletal red cell protein 4.1 R. " doi
  30. (1992). Defective Ca(2+)-induced microvesiculation and deficient expression of procoagulant activity in erythrocytes from a patient with a bleeding disorder: a study of the red blood cells of Scott syndrome. "
  31. (1999). Defective regulation of the epithelial Na+ channel by Nedd4 in Liddle's syndrome. " doi
  32. (2004). Defective trafficking of nephrin missense mutants rescued by a chemical chaperone. " doi
  33. (2003). Detergent resistant domains in erythrocyte membranes survive after cell cholesterol depletion: an EPR spin label study. " Chem Phys Lipids doi
  34. (2005). Detergent- res i stant membranes should not be identified with membrane rafts. " doi
  35. (2004). Detergents as tools for the purification and classification of lipid rafts. " doi
  36. (2004). Distribution of lipid raft markers in live cells. doi
  37. (2000). Dual palmitoylation of PSD-95 mediates its vesiculotubular sorting, postsynaptic targeting, and ion channel clustering. " doi
  38. (2004). Dynamic redistribution of raft domains as an organizing platform for signaling during cell chemotaxis. "
  39. (2004). Dynamics of putative raftassociated proteins at the cell surface. "
  40. (2005). Effect of stomatin-like protein 2 (SLP-2) gene on growth and proliferation of esophageal squamous carcinoma cell line TE12]. "
  41. (1998). Effects of cholesterol depletion by cycloclextrin on the sphingolipid microdomains of the plasma membrane. "
  42. (1971). Electrophoretic analysis of the major polypeptides of the human erythrocyte membrane. " doi
  43. (1996). Enhanced vesiculation exacerbates complement-dependent hemolysis in glucose-6-phosphate dehydrogenase deficient red blood cells. " doi
  44. (2000). Epithelial Na+ channels and stomatin are expressed in rat trigeminal mechanosensory neurons. " doi
  45. (2004). Erythrocyte detergent-resistant membrane proteins. their characterization and selective uptake during malarial infection. "
  46. (1997). Erythrocyte membrane vesiculation: model for the molecular mechanism of protein sorting. " doi
  47. (2004). Eukaryotic and prokaryotic stomatins: the proteolytic link. " doi
  48. (1999). Exclusion of the stomatin, alpha-adducin and beta-adducin loci in a large kindred with dehydrated hereditary stomatocytosis. " doi
  49. (2003). Exclusively targeting beta-secretase to lipid rafts by GPI-anchor addition upregulates beta-site processing of the amyloid precursor protein. " doi
  50. (2005). Formation of membrane-bound ring complexes by prohibitins in mitochondria. " doi
  51. (2004). Four new cases of stomatin-deficient hereditary stomatocytosis syndrome: association of the stomatin-deficient cryohydrocytosis variant with neurological dysfunction. " doi
  52. (2004). FtsH exists as an exceptionally large complex containing HfIKC in the plasma membrane of Escherichia coli. " doi
  53. (1997). Functional rafts in cell membranes. "
  54. (1999). Functionally different GPI proteins are organized in different domains on the neuronal surface. ". doi
  55. (1992). GAL4 fusion vectors for expression in yeast or mammalian cells. " doi
  56. (1988). GAL4-VP16 is an unusually potent transcriptional activator. " doi
  57. (1998). GPI-anchored proteins are organized in submicron domains at the cell surface. "
  58. (2001). Grimellec doi
  59. (2000). How cells handle cholesterol. " doi
  60. (1996). Human erythrocyte band 7.2b is preferentially labeled by a photoreactive phospholipid. " doi
  61. (2000). Identification and characterization of human SLP-2, a novel homologue of stomatin (band 7.2b) present in erythrocytes and other tissues. " doi
  62. (2002). Identification of a functional role for lipid asymmetry in biological membranes: Phosphatidylserine-skeletal protein interactions modulate membrane stability. " doi
  63. (2005). Identification of non-specific lipid transfer protein-1 as a calmodulin-binding protein in Arabidopsis. " doi
  64. (1987). Identification of polypeptides encoded by an Escherichia coli locus (hfIA) that governs the lysis-lysogeny decision of bacteriophage lambda. "
  65. (1993). Identification of the phosphorylation site on human erythrocyte band 7 integral membrane protein: implications for a monotopic protein structure. " doi
  66. (1998). In vitro incorporation of GPI-anchored proteins into human erythrocytes and their fate in the membrane. "
  67. (2003). In vivo imaging of C. elegans mechanosensory neurons demonstrates a specific role for the MEC-4 channel in the process of gentle touch sensation. " doi
  68. (2000). Insolubility of lipids in triton X-100-. physical origin and relationship to sphingolipid/cholesterol membrane domains (rafts). " doi
  69. (1997). Interaction of influenza virus haernagglutinin with sphingolipid-cholesterol membrane domains via its transmembrane domain. " doi
  70. (2004). Intramembrane proteolysis: theme and variations. " doi
  71. (1991). Isolation and partial characterization of the human erythrocyte band 7 integral membrane protein. " doi
  72. (1992). Isolation of cIDNA coding for an ubiquitous membrane protein deficient in high Na+, low K+ stomatocytic erythrocytes. "
  73. (2004). Jumping to rafts: gatekeeper role of bilayer elasticity. " doi
  74. (1998). Lactacystin, proteasome function, and cell fate. " doi
  75. (2002). LAT displacement from lipid rafts as a molecular mechanism for the inhibition of T cell signaling by polyunsaturated fatty acids. " doi
  76. (1992). Lateral diffusion and percolation in two-phase, two-component lipid bilayers. Topology of the solid-phase domains in-plane and across the lipid bilayer. " doi
  77. (1977). Lipid phase transitions and phase diagrams. 1. Lipid phase transitions. " doi
  78. (2004). Lipid raft proteins have a random distribution during localized activation of the T-cell receptor. " doi
  79. (2002). Lipid rafts and assembly of enveloped viruses. " doi
  80. (2002). Lipid rafts and insulin signaling. "
  81. (2005). Lipid rafts and regulation of the cytoskeleton during T cell activation. " doi
  82. (2005). Lipid rafts in plants. " doi
  83. (2004). Lipid rafts: feeling is believing. "
  84. (2004). Lipid rafts: heterogeneity on the high seas. " doi
  85. (2001). Localization of mutations leading to altered cell shape and anion transport in the crystal structure of the cytoplasmic domain of band 3. " Blood Cells Mol Dis 27(l): doi
  86. (2001). Mammalian prohibitin proteins respond to mitochondrial stress and decrease during cellular senescence. ". doi
  87. (1985). Measurement of protein using bicinchoninic acid. " doi
  88. MEC-2 regulates C. elegans DEG/ENaC channels needed for mechanosensation. " doi
  89. (2004). Membrane and raft association of reggie-1/flotillin-2: role of myristoylation, palmitoylation and oligomerization and induction of filopodia by overexpression. ". doi
  90. (1991). Membrane vesiculation protects erythrocytes from destruction by complement. "
  91. (1982). Missing band 7 membrane protein in two patients with high Na, low K erythrocytes. " doi
  92. (2005). Modulation of erythrocyte membrane mechanical function by protein 4.1 phosphorylation. " doi
  93. (2002). Molecular basis of red cell membrane disorders. " doi
  94. (2003). Molecular basis of the functional podocinnephrin complex: mutations in the NPHS2 gene disrupt nephrin targeting to lipid raft microdomains. ". doi
  95. (1998). Molecular cloning of hSLP-1, a novel human brain-specific member of the band 7/MEC-2 family similar to Caenorhabditis elegans UNC-24. " doi
  96. Normal erythrocyte calpain I activity on membrane proteins under near-physiological conditions in patients with essential hypertension. " Sao Paulo Med doi
  97. (1998). Nuclear access and action of notch in vivo. " doi
  98. (1995). Nuclear actin filaments and their topological changes in frog oocytes. "
  99. (1998). Oligomeric nature of the integral membrane protein stomatin. " doi
  100. (1997). On the origin of sphingolipid/cholesterol-rich detergent-insoluble cell membranes: physiological concentrations of cholesterol and sphingolipid induce formation of a detergentinsoluble, liquid-ordered lipid phase in model membranes. " doi
  101. (2001). Overexpression of stomatin depresses GLUT-1 glucose transporter activity. "
  102. (2003). Palm itoylation of phospholipid scramblase 1 controls its distribution between nucleus and plasma membrane. " doi
  103. (2005). Palmitoylation regulates plasma membrane-nuclear shuttling of R7131P, a novel membrane anchor for the RGS7 family. " doi
  104. (2005). Palmitoylation-dependent estrogen receptor alpha membrane localization: regulation by 17beta-estradiol. "
  105. (1997). Pathophysiologic implications of membrane phospholipid asymmetry in blood cells.
  106. (2002). Placental alkaline phosphatase is efficiently targeted to rafts in supported lipid bilayers. " doi
  107. (2001). Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin. " doi
  108. (2002). Prohibitin and prohibitone are contained in high-molecular weight complexes and interact with alpha-actinin and annexin A2. " doi
  109. (2005). Prohibitin is required for Ras-induced Raf-MEK-ERK activation and epithelial cell migration. " doi
  110. (1996). Prostaglandin E2 stimulates a Ca2+-dependent K+ channel in human erythrocytes and alters cell volume and filterability. " doi
  111. (2000). Protein 4.1, a multifunctional protein of the erythrocyte membrane skeleton: structure and functions in erythrocytes and nonerythroid cells. "
  112. (2000). Protein degradation in mitochondria. " doi
  113. (2002). Proteolytic processing of low density lipoprotein receptor-related protein mediates regulated release of its intracellular domain. " doi
  114. (2003). Proteomic characterisation of neuronal sphingolipid-cholesterol microdomains- role in plasminogen activation. " doi
  115. (2005). PTOV1 enables the nuclear translocation and mitogenic activity of flotillin-1, a major protein of lipid rafts. " doi
  116. (2004). Purification and characterization of the human erythrocyte band 3 protein C-terminal domain. " doi
  117. (1991). Purification of band 7.2b, a 31-kDa integral phosphoprotein absent in hereditary stomatocytosis. "
  118. (1997). Reconstitution of Ca(2 +)-dependent K+ transport in erythrocyte membrane vesicles requires a cytoplasmic protein. "
  119. (1987). Recovery of human neutrophils from complement attack: removal of the membrane attack complex by endocytosis and exocytosis. "
  120. (1999). Red blood cell membrane disorders. " doi
  121. (1986). Repolarization of the membrane potential of blood platelets after complement damage: evidence for a Ca++ -dependent exocytotic elimination of C5b-9 pores. "
  122. (2003). Resistance of cell membranes to different detergents. " doi
  123. (2003). Role of cholesterol in lipid raft formation. lessons from lipid model systems. " doi
  124. (2005). Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion protein. " doi
  125. (2005). Scaffolding microdomains and beyond: the function of reggie/flotillin proteins. " Cell Mol Life Sci 62(19-20): doi
  126. (2001). Seeing is believing: visualization of rafts in model membranes. " doi
  127. (2000). Selective accumulation of raft-associated membrane protein LAT in T cell receptor signaling assemblies. " doi
  128. (1996). Selfish operons: horizontal transfer may drive the evolution of gene clusters. "
  129. (1992). Sorting of GPI-anchored proteins to glycolipidenriched membrane subdomains during transport to the apical cell surface. " doi
  130. (2005). Spatial segregation of gamma-secretase and substrates in distinct membrane domains. "
  131. (2001). Spectrin and ankyrin-based pathways: metazoan inventions for integrating cells into tissues. "
  132. (2002). Splenectomy prolongs in vivo survival of erythrocytes differently in spectrin/ankyrin- and band 3-deficient hereditary spherocytosis. "
  133. (2002). Stomatin is a major lipid-raft component of platelet alpha granules. " doi
  134. (2005). Stomatin is mis-trafficked in the erythrocytes of overhydrated hereditary stomatocytosis, and is absent from normal primitive yolk sac-derived erythrocytes. " doi
  135. (2004). Stomatin modulates gating of acid-sensing ion channels. " doi
  136. (2001). Stomatin, flotillin-1, and flotillin-2 are major integral proteins of erythrocyte lipid rafts. " doi
  137. (1993). Stomatin: a putative cation transport regulator in the red cell membrane. " doi
  138. (1997). Stomatin. " doi
  139. Stomatocytosis is absent in "stomatin"-deficient murine red blood cells. "
  140. (1961). Stomatocytosis. a hereditary red cell anomally associated with haemolytic anaemia. " doi
  141. (2002). T-actin dynamics control segregation of the TCR signaling cascade to clustered lipid rafts. " doi
  142. (1999). Temperature effects on cation transport in hereditary stomatocytosis and allied disorders. " doi
  143. (2003). The "stomatin" gene and protein in overhydrated hereditary stomatocytosis. "
  144. (1996). The Caenorhabditis elegans behavioral gene unc-24 encodes a novel bipartite protein similar to both erythrocyte band 7.2 (stomatin) and nonspecific lipid transfer protein. " doi
  145. (2003). The calpain system. "
  146. (1995). The cows or the fence? ".
  147. (1999). The hereditary stomatocytoses and allied disorders: congenital disorders of erythrocyte membrane permeability to Na and K. " Baillieres Best Pract Res Clin Haematol doi
  148. (2004). The hereditary stomatocytoses'. genetic disorders of the red cell membrane permeability to monovalent cations. " doi
  149. (2005). The inner nuclear membrane protein Sunl mediates the anchorage of Nesprin-2 to the nuclear envelope. " i Cell Sci 118(Pt 15): doi
  150. (2004). The inner side of T cell lipid rafts. " doi
  151. (1980). The isolation and characterization of 60 nm vesicles ('nanovesicles') produced during ionophore A23187-induced budding of human erythrocytes. "
  152. (2002). The mitochondrial PHB complex: roles in mitochondrial respiratory complex assembly, ageing and degenerative disease. " doi
  153. (1999). The molecular basis of disorders of the red cell membrane. " doi
  154. (2002). The size of lipid rafts- an atomic force microscopy study of ganglioside GM1 domains in sphingomyelin/DOPC/cholesterol membranes. " doi
  155. (1999). The SPFH domain: implicated in regulating targeted protein turnover in stomatins and other membraneassociated proteins. " doi
  156. (1999). The structure, biosynthesis and functions of glycosylphosphatidylinositol anchors, and the contributions of trypanosome research. "
  157. (1996). Traffic, polarity, and detergent solubility of a g lycosylphos phatidyl i nos itol-an chored protein after LDL-deprivation of MDCK cells. "
  158. Transport mechanisms in Plasmodium-infected erythrocytes: lipid rafts and a tubovesicular network. " doi
  159. (2002). Triton promotes domain formation in lipid raft mixtures. " doi
  160. (2003). Tumor suppression by the prohibitin gene 3'untranslated region RNA in human breast cancer. " doi
  161. (2005). Turning cells red: signal transcluction mediated by erythropoietin. " doi
  162. (1998). Unc-1: a stomatin homologue controls sensitivity to volatile anesthetics in Caenorhabditis elegans. doi
  163. (1997). Use of cyclodextrins for manipulating cellular cholesterol content. "
  164. (2005). Viral entry, lipid rafts and caveosomes. " doi
  165. (2003). Visualization of protein compartmentation within the plasma membrane of living yeast cells. " doi
  166. (2001). Visualizing detergent resistant domains in model membranes with atomic force microscopy. " doi
  167. (2003). Visualizing lipid structure and raft domains in living cells with twophoton microscopy. " doi
  168. (2003). Zwaal doi

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.