Abstract
Traditionally regarded as a cytoplasmic scaffolding protein, desmin has recently been found to have nuclear functions alongside other intermediate filaments. Although several studies have reported desmin's nuclear localization under specific conditions, the mechanisms behind its transport into the nucleus and the functional outcomes remain unclear. Computational analyses identified two putative bipartite nuclear localization signals (NLSs) within desmin's sequence, suggesting it undergoes active nuclear import via the classical importin-α/β pathway. Analysis of GFP-fused deletion constructs in synchronized human skeletal myoblasts showed that disruption of these NLSs leads to a modest decrease in nuclear desmin levels, suggesting that they may contribute to nuclear localization Treatment with ivermectin, an inhibitor of the importin α/β pathway, resulted in a statistically significant but moderate reduction in nuclear desmin, supporting the notion that desmin translocation may involve karyopherin-dependent mechanisms. However, alternative karyopherin-independent transport mechanisms cannot be excluded, as the amphiphilic desmin may also directly interact with nucleoporins of the nuclear pore complex (NPC). Desmin contains two functional NLSs in its N-terminal and rod domains, mediating nuclear import. This nuclear transport is likely complex and may be regulated during myogenesis or cellular stress. Although subcellular fractionation is challenging due to desmin's biochemical properties and tight perinuclear association, the findings provide new insight that may be crucial in muscle physiology and pathologies.