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

Abstract

Fodrin and its erythroid-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, like various cancers and certain neuronal disorders. Fodrin and spectrin are two-chain (αβ) molecules that are encoded by paralogous genes and share many common 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+, calmoduln, and a variety of post-translational 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.

Interactomic exploration of LRRC8A in volume-regulated anion channels

“…SPTAN1 is a protein with an EF-hand domain that appears to be involved in secretion, and it interacts with calmodulin in a Ca 2+ -dependent manner. This interaction allows it to move the cytoskeleton across the membrane [ 109 ].…”

Serum Biomarkers for the Diagnosis of Glaucoma

“…In this study, serum anti-α-fodrin IgG antibody levels were lower in patients with glaucoma. α-Fodrin is an intracellular, actin-binding, organ-specific protein of the cytoskeleton and plays a crucial role in maintaining structural integrity in mammalian cells [ 36 ]. Antibodies against α-fodrin are associated with Sjögren’s syndrome [ 37 ] and neurodegenerative diseases [ 38 ].…”

Mechanical role of the submembrane spectrin scaffold in red blood cells and neurons

“…The assembled spectrin repeat is stable, with flexibility between repeats (DeSilva et al, 1997;Grum et al, 1999). Erythrocyte and non-erythrocyte spectrins have a similar organization (Sreeja et al, 2020) -α-spectrins have 21 repeats, with repeat 10 being different and connected to a SH3 domain. β-spectrins have 17 repeats, and a pair of calponin-homology domains at the amino-terminus that interacts with actin (Fig.…”