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

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

ACKNOWLEDGMENTS

We acknowledge the Department of Science and Technology-Science Education and Research Board, Government of India, for extramural funding and the Department of Biotechnology, Rajiv Gandhi Center for Biotechnology, India, for core funding. J.S.S. and D.D. were provided fellowships by the University Grants Commission, Government of India, and the Indian Council for Medical Research, Government of India.

J.S.S. and S.S. were involved in writing the manuscript, data analysis, and conceptualization. R.J., D.D., and R.K.N. contributed to writing, data analysis, and critical reading. S.S. supervised and provided the funding. All authors approved the final form.

We declare that there is no conflict of interest.