A Fresh Look at the Structure, Regulation, and Functions of Fodrin

Mol Cell Biol. 2020 Aug 14;40(17):e00133-20. doi: 10.1128/MCB.00133-20. Print 2020 Aug 14.

Abstract

Fodrin and its erythroid cell-specific isoform spectrin are actin-associated fibrous proteins that play crucial roles in the maintenance of structural integrity in mammalian cells, which is necessary for proper cell function. Normal cell morphology is altered in diseases such as various cancers and certain neuronal disorders. Fodrin and spectrin are two-chain (αβ) molecules that are encoded by paralogous genes and share many features but also demonstrate certain differences. Fodrin (in humans, typically a heterodimer of the products of the SPTAN1 and SPTBN1 genes) is expressed in nearly all cell types and is especially abundant in neuronal tissues, whereas spectrin (in humans, a heterodimer of the products of the SPTA1 and SPTB1 genes) is expressed almost exclusively in erythrocytes. To fulfill a role in such a variety of different cell types, it was anticipated that fodrin would need to be a more versatile scaffold than spectrin. Indeed, as summarized here, domains unique to fodrin and its regulation by Ca2+, calmodulin, and a variety of posttranslational modifications (PTMs) endow fodrin with additional specific functions. However, how fodrin structural variations and misregulated PTMs may contribute to the etiology of various cancers and neurodegenerative diseases needs to be further investigated.

Keywords: apoptosis; cell signaling; cytoskeleton; drug interactions; mitosis.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Animals
  • Calcium / metabolism
  • Calmodulin / metabolism
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Erythroid Cells / metabolism
  • Humans
  • Microfilament Proteins / chemistry*
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism*
  • Neurons / metabolism
  • Spectrin / metabolism
  • Spectrin / physiology
  • Structure-Activity Relationship

Substances

  • Actins
  • Calmodulin
  • Carrier Proteins
  • Microfilament Proteins
  • fodrin
  • Spectrin
  • Calcium