Nuclear localization signal in Leishmania spp.: Implications for parasite physiology and host nucleus hijacking

Protein transport between the cytoplasm and the nucleus is a fundamental process for the survival and proper functioning of all eukaryotic cells. This transport is regulated by adaptor proteins that recognize nuclear localization signals (NLSs) present in essential nuclear proteins. The data compiled in this review provide an overview of the classification and diversity of NLSs across various organisms. As in all eukaryotes, NLS-mediated transport is essential for Leishmania spp. For this parasite, there is evidence that NLS-mediated transport is essential for its physiology, allowing key proteins to perform crucial functions in maintaining intrinsic nuclear processes. Beyond classical nuclear proteins, this review indicates that some Leishmania proteases also contain NLSs, suggesting that these enzymes may have multifaceted roles: acting within the parasite itself and functioning as a strategy by the parasite to modulate the nuclear dynamics of the host cell. NLS-tagged metalloproteases of the GP63 family are known to interact with host nuclear components and inactivate critical transcription factors, thereby modulating cellular responses and promoting parasite survival. This function persists during the parasite's differentiation from the promastigote to the amastigote form, highlighting a continuous and sophisticated survival strategy. However, this mechanism still requires experimental confirmation. A deeper understanding of these processes offers promising perspectives for the development of novel therapeutic approaches against leishmaniasis.