Evolution of spectrin function in cytoskeletal and membrane networks

Biochem Soc Trans. 2009 Aug;37(Pt 4):796-803. doi: 10.1042/BST0370796.


Spectrin is a cytoskeletal protein thought to have descended from an alpha-actinin-like ancestor. It emerged during evolution of animals to promote integration of cells into tissues by assembling signalling and cell adhesion complexes, by enhancing the mechanical stability of membranes and by promoting assembly of specialized membrane domains. Spectrin functions as an (alphabeta([H]))(2) tetramer that cross-links transmembrane proteins, membrane lipids and the actin cytoskeleton, either directly or via adaptor proteins such as ankyrin and 4.1. In the present paper, I review recent findings on the origins and adaptations in this system. (i) The genome of the choanoflagellate Monosiga brevicollis encodes alpha-, beta- and beta(Heavy)-spectrin, indicating that spectrins evolved in the immediate unicellular precursors of animals. (ii) Ankyrin and 4.1 are not encoded in that genome, indicating that spectrin gained function during subsequent animal evolution. (iii) Protein 4.1 gained a spectrin-binding activity in the evolution of vertebrates. (iv) Interaction of chicken or mammal beta-spectrin with PtdInsP(2) can be regulated by differential mRNA splicing, which can eliminate the PH (pleckstrin homology) domain in betaI- or betaII-spectrins; in the case of mammalian betaII-spectrin, the alternative C-terminal region encodes a phosphorylation site that regulates interaction with alpha-spectrin. (v) In mammalian evolution, the single pre-existing alpha-spectrin gene was duplicated, and one of the resulting pair (alphaI) neo-functionalized for rapid make-and-break of tetramers. I hypothesize that the elasticity of mammalian non-nucleated erythrocytes depends on the dynamic rearrangement of spectrin dimers/tetramers under the shearing forces experienced in circulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Ankyrins / classification
  • Ankyrins / genetics
  • Ankyrins / metabolism
  • Cytoskeletal Proteins / classification
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Evolution, Molecular*
  • Membrane Proteins / classification
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Models, Biological
  • Phylogeny
  • Spectrin / classification*
  • Spectrin / genetics
  • Spectrin / metabolism*


  • Ankyrins
  • Cytoskeletal Proteins
  • Membrane Proteins
  • Spectrin