Profilin Isoforms in Health and Disease – All the Same but Different

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).