Plastin family of actin-bundling proteins: its functions in leukocytes, neurons, intestines, and cancer

Abstract

Sophisticated regulation of the actin cytoskeleton by a variety of actin-binding proteins is essential for eukaryotic cells to perform their diverse functions. The plastin (also know, as fimbrin) protein family belongs to actin-bundling proteins, and the protein family is evolutionarily conserved and expressed in yeast, plant, and animal cells. Plastins are characterized by EF-hand Ca(2+)-binding domains and actin-binding domains and can cross-link actin filaments into higher-order assemblies like bundles. Three isoforms have been identified in mammals. T-plastin is expressed in cells from solid tissues, such as neurons in the brain. I-plastin expression is restricted to intestine and kidney; the isoform plays a vital role in the function of absorptive epithelia in these organs. L-plastin is expressed in hematopoietic cell lineages and in many types of cancer cells; the isoform is thus considered to be a useful biomarker for cancer.

Figure 1

Human and mouse plastin isoforms. The homology between the amino acid sequences of these isoforms is showed.

Figure 2

Schematic diagram of L-plastin structure. (a) Domain organization of L-plastin. The protein possesses an N-terminal headpiece of ~100 amino acids containing two EF-hand Ca²⁺-binding motifs and two actin-binding domains (ABDs) consisting of ABD1 (residues 120–379) and ABD2 (residues 394–623), and each ABD contains two calponin-homology (CH) domains. (b) Reconstructed molecular shape of L-plastin. Conformational analyses of L-plastin by X-ray scattering in solution revealed that plastin has a compact globular structure rather than a dumbbell-like shape. It is conceivable that the two ABDs are packed together in an approximately antiparallel arrangement with the N- and C-terminal CH domains (CH1 and CH4) making direct contact as shown in Figure 2(c); that is, X, Y, and Z correspond to CH1–CH3, CH2–CH4, and CH3-CH4 of the plastin protein, respectively. P indicates a putative N-terminal headpiece. See more details in [6, 7]. (c) Possible arrangement of the ABDs (CH1–CH4) of L-plastin in solution without Ca²⁺.