Diversification of the calponin family proteins by gene amplification and repeat expansion of calponin-like motifs

Abstract

The calponin family proteins in vertebrates, including calponin and transgelin (also known as SM22 or NP25), regulate actin-myosin interaction and actin filament stability and are involved in regulation of muscle contractility and cell migration. Related proteins are also present in invertebrates and fungi. Animals have multiple genes encoding calponin family proteins with variable molecular features, which are often expressed in the same tissues or cells. However, functional studies of this class of proteins have been reported only in limited species. Through database searches, I found that the calponin family proteins were diversified in animals by gene amplification and repeat expansion of calponin-like (CLIK) motifs, which function as actin-binding sequences. Transgelin-like proteins with a single CLIK motif are the most primitive type and present in fungi and animals. In many animals, additional calponin family proteins containing multiple CLIK motifs, as represented by vertebrate calponins with three CLIK motifs, are present. Interestingly, in several invertebrate species, there are uncharacterized calponin-related proteins with highly expanded repeats of CLIK motifs (up to 23 repeats in mollusks). These variable molecular features of the calponin family proteins may be results of evolutionary adaptation to a broad range of cell biological events.

Keywords: actin; calponin; calponin-like motifs; muscle contraction; transgelin.

Figure 1.

Schematic representation of structures of the calponin family proteins. Domain structures of previously characterized calponin family proteins (A) and related proteins reported only in sequence databases (B). Orange rounded rectangles are calponin homology (CH) domains, and green ellipses (indicated as CALP^~) are CLIK motifs. Bar, 100 amino acids. Graphics were obtained from PROSITE (Sigrist et al. 2010) and annotated using Adobe Illustrator CS3.

Figure 2.

Alignment of CLIK motifs from representative calponin family proteins (A) and 23 CLIK motifs from the freshwater snail Biomphalaria glabrata A0A2C9K5U7, including three CLIK motifs from human calponin-1 (CNN1) for comparison (B). Amino acids are colored based on the chemical properties of side chains as indicated on the figure. The sequences were aligned with MUSCLE (Edgar 2004) using MegAlign Pro (DNASTAR, Inc). See Supplemental Figure S1 for alignment of 196 CLIK motifs.