An F-actin- and calmodulin-binding protein from isolated intestinal brush borders has a morphology related to spectrin

Properties of brain spectrin (fodrin)

“…It is already known [4,6] that tetrameric fodrin will bind to and cross-link F-actin. In the case of human red cell spectrin [8] (though not necessarily that from other species, such as the sheep [22]), binding to F-actin is very weak, unless the cytoskeletal constituent, protein 4.1 is present.…”

“…In this light, it is reassuring that the structural characteristics of the two proteins, on which the mechanical properties conferred by the cytoskeletal network on the membrane must depend, are similar, and also that the pattern of functionally important interactions is conserved. It should be borne in mind that fodrin also retains the property of binding to ankyrin, the membraneattachment protein for spectrin [4,7], as well as to calmodulin [4,5].…”

“…Proteins, immunologically related to spectrin and sharing certain of its physical characteristics, have been isolated from brain and from intestinal microvilli [6]. They contain two different polypeptide chains, resemble spectrin in the electron microscope, though the contour length of brain spectrin (termed fodrin [4] or calspectin [3]) appears to be appreciably greater than that of red cell spectrin 151, and they bind calmodulin and F-actin [3-51, as well as, in the case of fodrin, attaching to the spectrin binding sites (ankyrin) on red cell membrane vesicles [4,7].…”

“…Nevertheless, the extent of the structural and functional similarity of spectrin to fodrin is not established. Thus for example, fodrin exists as a tetramer, difficult to dissociate into its constituent dimers under nondenaturing conditions [4,5], whereas spectrin tetramers dissociate readily into their heterodimer parts; fodrin appears to bind strongly to F-actin, whereas human spectrin at least binds only weakly in the absence of a third cytoskeletal protein, 4.1 [8], Moreover, attention has in the past been drawn to the similarity of gross shape of spectrin to a number of other actin-binding proteins [9], that in other respects appear to be unrelated. One unusual structural feature of spectrin, the very high a-helix content (70-80%), is not shared by these proteins, and indeed a high-Mr species that cross-reacts immunologically with spectrin, and was thought to belong to the same class, has been reported to have a vanishingly low cu-helicity [lo].…”

Functional diversity among spectrin isoforms

“…The direct visualization of ankyrin [Davis and Bennett, 1984b], calmodulin [Tsukita et al, 19831, and antigenic sites [Glenney et al, 1983al on mammalian brain spectrin and the mapping of human brain spectrin functional domains [Harris and Morrow, 1988b;Harris et al, 19881 indicate that these tetramers are arranged in an erythroid-like head-to-head manner. Given the similar composition and morphology of other nonerythroid spectrins, it is likely that all spectrin tetramers are arranged in a similar Bennett [ 19851;3, Bloch and Morrow [1989]; 4, Branton et al [1981]; 5, Byers et al [ 19871;6 , Coleman et al [1989]; 7, Dubreuil et al [1987]; 8, Fishkind et al [1987]; 9, Giebelhaus et al 119871;10, Glenney and Glenney [1983a]; 11, ; 12, Glenney et al [1982b]; 13, ; 14, Goodman and Zagon [1986]; 15, Kuramochi et al [1986]; 16, Lazarides and Nelson [1985]; 17, Marchesi [1985]; 18, ; 19, Pearl et al [1984];20, Pollard 119841;21, Shatten et al [1986]; 22, Shile et al [1985]; 23, Repasky et al [1982]; 24, Riederer et al [1986].…”