Profilin Isoforms in Health and Disease - All the Same but Different.

Kai Murk,Marta Ornaghi,Juliane Schiweck

doi:10.3389/fcell.2021.681122

Kai Murk, Marta Ornaghi + Show 1 more

Open Access

https://doi.org/10.3389/fcell.2021.681122

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Abstract

Profilins are small actin binding proteins, which are structurally conserved throughout evolution. They are probably best known to promote and direct actin polymerization. However, they also participate in numerous cell biological processes beyond the roles typically ascribed to the actin cytoskeleton. Moreover, most complex organisms express several profilin isoforms. Their cellular functions are far from being understood, whereas a growing number of publications indicate that profilin isoforms are involved in the pathogenesis of various diseases. In this review, we will provide an overview of the profilin family and “typical” profilin properties including the control of actin dynamics. We will then discuss the profilin isoforms of higher animals in detail. In terms of cellular functions, we will focus on the role of Profilin 1 (PFN1) and Profilin 2a (PFN2a), which are co-expressed in the central nervous system. Finally, we will discuss recent findings that link PFN1 and PFN2a to neurological diseases, such as amyotrophic lateral sclerosis (ALS), Fragile X syndrome (FXS), Huntington’s disease and spinal muscular atrophy (SMA).

Highlights

Over forty years ago, the first profilin was identified as a small actin monomer binding protein with the ability to inhibit actin polymerization in vitro (Carlsson et al, 1977)
When we reviewed the regulation of actin dynamics by “profiling,” we discussed studies using either yeast profilin or mammalian profilin 1
Reduced SMN levels affect posttranslational modifications of Profilin 2a (PFN2a): This profilin isoform is hyper-phosphorylated at multiple sites within its PLP-binding site, when SMN is depleted in cell lines and in spinal cords of a spinal muscular atrophy (SMA) mouse model (Nölle et al, 2011)

Summary

Introduction

Over forty years ago, the first profilin was identified as a small actin monomer binding protein with the ability to inhibit actin polymerization in vitro (Carlsson et al, 1977). These experimental findings are supported by structural data showing all residues central to actin binding are conserved between PFN1 and PFN2a (Figures 3A,D). PFN1 and PFN2a possess mutual as well as isoform-specific functions in the CNS, which regulate multiple processes including membrane trafficking and shaping of the plastic morphology of neuronal cells.

Results

Conclusion