The emergence of nebulin repeats and evolution of lasp family proteins

Abstract

The LIM and SH3 domain protein (lasp) family, the smallest proteins in the nebulin superfamily, consists of vertebrate lasp‐1 expressed in various non‐muscle tissues, vertebrate lasp‐2 expressed in the brain and cardiac muscle, and invertebrate lasp whose functions have been analyzed in Ascidiacea and Insecta. Gene evolution of the lasp family proteins was investigated by multiple alignments, comparison of gene structure, and synteny analyses in eukaryotes in which mRNA expression was confirmed. All invertebrates analyzed in this study belonging to the clade Filasterea, with the exception of Placozoa, have at least one lasp gene. The minimal actin‐binding region (LIM domain and first nebulin repeat) and SH3 domain detected in vertebrate lasp‐2 were found to be conserved among the lasp family proteins, and we showed that nematode lasp has actin‐binding activity. The linker sequences vary among invertebrate lasp proteins, implying that the lasp family proteins have universal and diverse functions. Gene structures and syntenic analyses suggest that a gene fragment encoding two nebulin repeats and a linker emerged in Filasterea or Holozoa, and the first lasp gene was generated following combination of three gene fragments encoding the LIM domain, two nebulin repeats with a linker, and the SH3 domain.

LASP1 in Cellular Signaling and Gene Expression: More than Just a Cytoskeletal Regulator

“…Despite a nuclear export signal, LASP1 is reliant on a nuclear shuttle partner–the tight junction protein zona occludens 2 (ZO2) and potentially AKT1. Phosphorylation of LASP1 at S146 releases the protein from the cytoskeleton (shown for actin and zyxin) and allows the re-localization of the LASP1-ZO2 complex from the outer cell membrane into the nucleus [ 7 ]. In contrast to solid tumors, CML cells show low levels of ZO2 and therefore no nuclear LASP1 localization was detected.…”

“…The first nebulin repeat includes a nuclear export signal (NES; aa 71–77) [ 6 ]. A recent molecular evolutionary analysis of vertebrate and invertebrate lasp family proteins revealed that all proteins harbor the same ancestral gene and that the LIM domain, nebulin repeats and SH3 domain are highly conserved between both groups, although the invertebrate lasp linker sequences vary [ 7 ].…”