Types of nuclear localization signals and mechanisms of protein import into the nucleus

Juane Lu,Jianjun Qiao,Suke Liu,Biao Zhang,Haihua Ruan,Wenjun Song,Tao Wu

doi:10.1186/s12964-021-00741-y

Abstract

Nuclear localization signals (NLS) are generally short peptides that act as a signal fragment that mediates the transport of proteins from the cytoplasm into the nucleus. This NLS-dependent protein recognition, a process necessary for cargo proteins to pass the nuclear envelope through the nuclear pore complex, is facilitated by members of the importin superfamily. Here, we summarized the types of NLS, focused on the recently reported related proteins containing nuclear localization signals, and briefly summarized some mechanisms that do not depend on nuclear localization signals into the nucleus.9b35b5XrF5YBVYeQB6JADFVideo

Highlights

One of the characteristic features of eukaryotic cells are membrane-bound functional organelles such as the nucleus, mitochondria, golgi apparatus, and others, which are surrounded by cytoplasm
This region acts as an interacting domain for the nuclear export factor Nuclear export factor dependent on importin α (CAS), known as Cse1, and nucleoporin 50 (Nup50, referred to as Npap60), which catalyze cargo dissociation and function as molecular ratchets that prevent futile cycles, allowing importin α to combine with RanGTP to be exported from the nucleus [46, 57]
NLS nuclear localization signal, NPC nuclear pore complex. This observation is the first evidence that importin α within the trimeric complex actively contributes to the efficiency of classical nuclear localization signals (cNLS)-mediated cargo transport. These findings suggest that importin α serves as an adaptor molecule between the cargo and importin β1, and actively contributes to NPC-mediated translocation by the trimeric cNLS-cargo-importin α-importin β1 complex [2, 47]

Summary

Background

One of the characteristic features of eukaryotic cells are membrane-bound functional organelles such as the nucleus, mitochondria, golgi apparatus, and others, which are surrounded by cytoplasm. MP NLS are a single cluster composed of 4–8 basic amino acids, which generally contains 4 or more positively charged residues, that is, arginine (R) or lysine (K). If the third amino acid lysine (K) of SV40 large T antigen NLS is mutated to threonine (T), its nuclear transport function is lost [18]. Willis et al identified a putative NLS (640PKLKRQ646) in vasopressin-activated calcium-mobilizing protein/cullin (VACM-1/CUL5), which is necessary for its nuclear localization and inhibitory effect on cellular growth. This sequence starts with a proline (P) and is followed by an amino acid sequence containing three basic residues out of four (PKLKR) [19].

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Findings

Conclusions and perspectives