New Findings on LMO7 Transcripts, Proteins and Regulatory Regions in Human and Vertebrate Model Organisms and the Intracellular Distribution in Skeletal Muscle Cells

Abstract

LMO7 is a multifunctional PDZ–LIM protein that can interact with different molecular partners and is found in several intracellular locations. The aim of this work was to shed light on LMO7 evolution, alternative transcripts, protein structure and gene regulation through multiple in silico analyses. We also explored the intracellular distribution of the LMO7 protein in chicken and zebrafish embryonic skeletal muscle cells by means of confocal fluorescence microscopy. Our results revealed a single LMO7 gene in mammals, sauropsids, Xenopus and in the holostean fish spotted gar while two lmo7 genes (lmo7a and lmo7b) were identified in teleost fishes. In addition, several different transcripts were predicted for LMO7 in human and in major vertebrate model organisms (mouse, chicken, Xenopus and zebrafish). Bioinformatics tools revealed several structural features of the LMO7 protein including intrinsically disordered regions. We found the LMO7 protein in multiple intracellular compartments in chicken and zebrafish skeletal muscle cells, such as membrane adhesion sites and the perinuclear region. Curiously, the LMO7 protein was detected within the nuclei of muscle cells in chicken but not in zebrafish. Our data showed that a conserved regulatory element may be related to muscle-specific LMO7 expression. Our findings uncover new and important information about LMO7 and open new challenges to understanding how the diverse regulation, structure and distribution of this protein are integrated into highly complex vertebrate cellular milieux, such as skeletal muscle cells.

Transmembrane Membrane Readers form a Novel Class of Proteins That Include Peripheral Phosphoinositide Recognition Domains and Viral Spikes

“…In contrast, our MODA analysis predicts that the 1.46 Å resolution crystal structure of the LIM only protein 7 (LMO7) PDZ domain solved by S. Yokoyama's group contains a major phospholipid bilayer docking site, which is only partially apparent in the AlphaFold2 model (Figure 4). The lipid specificities of the PDZ domains of PDZD8, LMO7 [51] and the protease Htra2 [50] remain unclear. However, PDZ-lipid interactions could contribute to the localization of LMO7 to the PM and nuclear envelop, where it plays a role in cell differentiation.…”