Evidence that the phosphatidylinositol cycle is linked to cell motility

Lassing, Ingrid; Lindberg, Uno

doi:10.1016/0014-4827(88)90136-x

Cited by 126 publications

(45 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In nucleated cells, it is commonly held that membrane PtdIns(4,5)P2 turnover may affect cytoskeletal dynamics during cell activation [60]. Erythrocyte band 4.1 is known to have immunoreactive analogues in a wide variety of nonerythroid cells (reviewed in [2]), and recently has been shown to have sequence similarity with the cytoskeletal proteins ezrin and talin [61], moesin [62] and radixin [63].…”

Section: Discussionmentioning

confidence: 99%

The role of inositol phospholipids in the association of band 4.1 with the human erythrocyte membrane

Gascard

Pawełczyk

Lowenstein

et al. 1993

European Journal of Biochemistry

View full text Add to dashboard Cite

Band 4.1 is a major protein of the erythrocyte membrane skeleton. It promotes the binding of spectrin to F-actin and may anchor the skeletal network to the plasma membrane via its association with integral membrane proteins. Here, we have investigated the involvement of inositol phospholipids in the binding of band 4.1 to erythrocyte membranes using membrane vesicles stripped of all peripheral proteins at alkaline pH. Trypsinization of these vesicles allows the discrimination of two classes of band 4.1 binding sites: trypsin-sensitive sites (60-65 % of the total), largely or exclusively on band 3, and trypsin-resistant sites (35-40% of the total), composed, at least in part, of the glycophorins. ATP depletion or activation of erythrocyte phosphoinositol phospholipase C led to a reduction in membrane phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] content by 20-70% in different experiments. The resulting decrease of band 4.1 binding to vesicles by was variable, but averaged about 15-20%. The same treatments led to an average decrease in the band 4.1 binding capacity of trypsinized vesicles of 55%. Since this is equivalent to a 20% decrease in the binding capacity of non-trypsinized vesicles (consistent with the above result), it indicates that PtdIns(4,5)P2 regulates the binding of band 4.1 only to trypsin-resistant binding sites (and to only a subset of these) accounting for about 1 5 2 0 % of total band 4.1 binding sites on membranes. We found that hydrolysis of > 95% of PtdIns(4,5)P2 with exogenous phospholipase C-6 (PLCG) resulted in no further decrease in band 4.1 binding to vesicles than did hydrolysis of 65-70% of PtdIns(4,5)P2 which is accessible to erythrocyte phosphoinositol phospholipase C. This suggests that only 65-70% of total membrane PtdIns(4,5)P2 is involved in regulating band 4.1 binding. Significantly, the pool of PtdIns(4,5)P, involved is the same pool which can be hydrolysed by erythrocyte phosphoinositol phospholipase C, and which has been shown to be metabolically labile in erythrocytes. The membrane binding capacity for band 4.1 found in this study (averaging 1000 pg/mg vesicle protein) is considerably higher than that found in previous studies. The results are consistent with the existence of a binding site for band 4.1 on each copy of the major transmembrane proteins (band 3 and the glycophorins). These results provide new insights into the involvement of membrane inositol phospholipids in cytoskeletal-membrane interactions.The human erythrocyte membrane is underlaid by a network of proteins that confers on the cell its characteristic biconcave shape, remarkable deformability and mechanical strength (reviewed in [I, 21). This network is mainly composed of spectrin tetramers, short oligomers of actin, and band 4.1, which self-assemble in complexes to form the skeletal lattice structure. Other proteins such as band 4.9, adduCorrespondence to

show abstract

Section: Discussionmentioning

confidence: 99%

The role of inositol phospholipids in the association of band 4.1 with the human erythrocyte membrane

Gascard

Pawełczyk

Lowenstein

et al. 1993

European Journal of Biochemistry

View full text Add to dashboard Cite

show abstract

“…Thus the b-thymosins allow at resting conditions the maintenance of a considerably higher intracellular concentration of monomeric actin than the C c of the pointed-end. The intracellular concentration of profilin-another G-actin binding/sequestering protein-is considerably lower (about 50 lM) and under resting conditions most of the profilin is inactivated by binding to PIP2 present in the cytoplasmic monolayer of the plasma membrane [Lassing and Lindberg, 1998]. …”

Section: Binding Of B-thymosins To Monomeric Actin Inhibits Polymerizmentioning

confidence: 99%

The β‐thymosins: Intracellular and extracellular activities of a versatile actin binding protein family

Mannherz

Hannappel

2009

Cell Motil. Cytoskeleton

109

View full text Add to dashboard Cite

The b-thymosins are N-terminally acetylated peptides of about 5 kDa molecular mass and composed of about 40-44 amino acid residues. The first member of the family, thymosin b4, was initially isolated from thymosin fraction 5, prepared in five steps from calf thymus. Thymosin b4 was supposed to be specifically produced and released by the thymic gland and to possess hormonal activities modulating the immune response. Various paracrine effects have indeed been reported for these peptides such as cardiac protection, angiogenesis, stimulation of wound healing, and hair growth. Besides these paracrine effects, it was noted that b-thymosins occur in high concentration in the cytoplasm of many eukaryotic cells and bind to the cytoskeletal component actin. Subsequently it became apparent from in vitro experiments that they preferentially bind to monomeric (G-)actin and stabilize it in its monomeric form. Due to this ability the b-thymosins are the main intracellular actin sequestering factor, i.e., they posses the ability to remove monomeric actin from the dynamic assembly and disassembly processes of the actin cytoskeleton that constantly occur in activated cells. In this review we will concentrate on the intracellular activity and localization of the b-thymosins, i.e., their modulating effect on the actin cytoskeleton. Cell Motil. Cytoskeleton 66: 839-851, 2009. '

show abstract

Section: Introductionmentioning

confidence: 99%

“…The actin-binding protein, profllin, is implicated in the regulation of actin polymerization [l] and the hydrolysis of phosphatidylinositol- (4,5)-bisphosphate (PIP2) [2,3]. These functions of profilin link the dynamics of the microfilament system to processes involved in transmembrane signalling and may be part of the mechanisms behind the immediate mobilization of the microfllament system upon stimulation of cells with growth factors like epidermal growth factor and platelet-derived growth factor [4]. Direct evidence for the involvement of profilin in the early phase of cell signalling comes from studies of platelets where the dramatic morphological change caused by thrombin stimulation is initiated by the dissociation of the profilinactin complex with extensive formation of actin filaments as a consequence [5].…”

Section: Introductionmentioning

confidence: 99%

Mutagenesis of human profilin locates its poly(l‐prolme)‐bindmg site to a hydrophobic patch of aromatic amino acids

et al. 1993

View full text Add to dashboard Cite

The actin-binding protein, profilin, contains a src-homology (SH) 3-like fold (Schutt, C.E. et al., submitted), and its tight interaction with poly(L-proline) is reminiscent of the binding activity exhibited by SH3-domains. Here we demonstrate that replacements of aromatic amino acids in a hydrophobic patch on the surface of the protilin molecule abolish its poly(L-proline)-binding capacity. However, the location of this hydrophobic patch is found in another region of the molecule than that displaying structural similarities with SH3 domains.

show abstract

Evidence that the phosphatidylinositol cycle is linked to cell motility

Cited by 126 publications

References 76 publications

The role of inositol phospholipids in the association of band 4.1 with the human erythrocyte membrane

The role of inositol phospholipids in the association of band 4.1 with the human erythrocyte membrane

The β‐thymosins: Intracellular and extracellular activities of a versatile actin binding protein family

Mutagenesis of human profilin locates its poly(l‐prolme)‐bindmg site to a hydrophobic patch of aromatic amino acids

Contact Info

Product

Resources

About