Spectrin and phospholipids — the current picture of their fascinating interplay

Abstract

Abbreviations used: ABD -actin-binding domain; AE1 -anion exchanger 1; Ankankyrin; CH -calponin homology domain; GPC -glycophorin C; MPP1 -membrane palmitoylated protein 1; PC -phosphatidylcholine; PE -phosphatidylethanolamine; PHpleckstrin homology domain; PI -phosphatidylinositol; PI(4,5)P 2 -phosphatidylinositol-4,5-bisphosphate; PS -phosphatidylserine; SH3 -SRC homology 3 domain; UPA -Unc5-PIDD-ankyrin domain; ZU5 -domain present in ZO-1 and Unc5-like netrin receptors Abstract: The spectrin-based membrane skeleton is crucial for the mechanical stability and resilience of erythrocytes. It mainly contributes to membrane integrity, protein organization and trafficking. Two transmembrane protein macro-complexes that are linked together by spectrin tetramers play a crucial role in attaching the membrane skeleton to the cell membrane, but they are not exclusive. Considerable experimental data have shown that direct interactions between spectrin and membrane lipids are important for cell membrane cohesion. Spectrin is a multidomain, multifunctional protein with several distinctive structural regions, including lipid-binding sites within CH tandem domains, a PH domain, and triple helical segments, which are excellent examples of ligand specificity hidden in a regular repetitive structure, as recently shown for the ankyrin-sensitive lipid-binding domain of beta spectrin. In this review, we summarize the state of knowledge about interactions between spectrin and membrane lipids.

Dances with Membranes: Breakthroughs from Super-resolution Imaging

“…We instead briefly discuss some regulatory influences of the anionic membrane phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP2). By binding to PIP2, ABPs can be targeted to membranes (e.g., spectrin; see review in ( Boguslawska, Machnicka, Hryniewicz-Jankowska, & Czogalla, 2014 ), ezrin/radixin/moesin proteins and talin ( Barret et al., 2000 , Hao et al., 2009 , Jayasundar et al., 2012 , Saltel et al., 2009 ) and annexins ( Hayes et al., 2009 , Martin-Belmonte and Mostov, 2007 )). PIP2 binding is also considered a necessary step in the activation of many ABPs ( Wu et al., 2014 ), such as ezrin/radixin/moesin proteins ( Yonemura, Matsui, & Tsukita, 2002 ), and Arp2/3 (via WASP) ( Higgs & Pollard, 2000 ).…”

Membrane Rafts in the Erythrocyte Membrane: A Novel Role of MPP1p55

“…Also, direct interactions of membrane skeletal proteins with membranelipids have been implied by numerous works (for reviews, see e.g. (Hanus-Lorenz et al 2001 ;Boguslawska et al 2014 ). Such data might contribute to establishing the link between detergent-resistant membranes and MPP1.…”

Proteins Regulating Microvesicle Biogenesis and Multidrug Resistance in Cancer

“…This observation suggests these direct PS‐cytoskeleton interactions are coupled with membrane–protein–cytoskeletal interactions—forming sizeable “adhesion patches” at spectrin junctions . Moreover, the distribution of phospholipid binding sites in the β‐spectrin near the sites of attachment of either ankyrin or protein 4.1 suggests PS may modulate the protein–protein interactions in erythroid and non‐erythroid membranes . Manno, Takakuwa, and Mohandas also demonstrated the significance of inner leaflet PS in experiments comparing red blood cell membranes, one in which asymmetric distribution of phospholipids was maintained and the other which had the phospholipids scrambled.…”