Importin α: a key molecule in nuclear transport and non-transport functions

Abstract

Importin α performs the indispensable role of ferrying proteins from the cytoplasm into the nucleus with a transport carrier, importin β1. Mammalian cells from mouse or human contain either six or seven importin α subtypes, respectively, each with a tightly regulated expression. Therefore, the combination of subtype expression in a cell defines distinct signaling pathways to achieve progressive changes in gene expression essential for cellular events, such as differentiation. Recent studies reveal that, in addition to nucleocytoplasmic transport, importin αs also serve non-transport functions. In this review, we first discuss the physiological significance of importin α as a nuclear transport regulator, and then focus on the functional diversities of importin αs based on their specific subcellular and cellular localizations, such as the nucleus and plasma membrane. These findings enrich our knowledge of how importin αs actively contribute to various cellular events.

Importin α-importin β complex mediated nuclear translocation of insulin-like growth factor binding protein-5

“…This is probably due to compensation by other importin-αs when we knockdown importin-α5, since there are five ubiquitously expressed importin-αs. While there is only one importin-β, so no compensation has been found when we inhibited importin-α/β pathway with importin-β dominant negative mutant [11,24].…”

“…The resulting trimeric complex then docks to the cytoplasmic periphery of the nuclear pore complexes (NPC), and is subsequently translocated to the nuclear side of the NPC [8,11,19]. To determine whether the interaction between importin-α5 and IGFBP-5 is result to the IGFBP-5 nuclear import, we investigated the subcellular localization of EGFP-tagged IGFBP-5 with (hIGFBP-5-EGFP) or without (mIGFBP-5-EGFP) signal peptide by confocal microscopy ( Fig.…”

“…Herein, we use yeast two hybrid to screen IGFBP-5 binding partner and find that importin-α5 interacts with IGFBP-5. Given that importin-α family is one of the component of the best understood system for the transport of macromolecules between the cytoplasm and the nucleus [11,24]. Defined by the primary amino acid similarities, Importin-αs are classified into three subfamilies in human (clade 1 to 3), and importin-α5 is referred to clade α1 with importin-α6, and α7.…”

“…Defined by the primary amino acid similarities, Importin-αs are classified into three subfamilies in human (clade 1 to 3), and importin-α5 is referred to clade α1 with importin-α6, and α7. Importin-α5 have been demonstrated that mediated the nuclear translocation of some protein, like NF-κB, STAT3 etc, and the expression of importin-α5 in human cells could be regulated by miR233 [11]. GST pull-down and co-IP were carried out to confirm the interaction between importin-α5 and IGFBP-5.…”

“…Mouse and human cells contain six and seven importin-α subtypes, and only one importin-β1. Acts as an adapter, importin-α binding to the NLS of cytosolic proteins, including IGFBP-5, as well as to the transport carrier, importin-β1 [11]. Research in IGFBP-5 nuclear import was analyzed and contradictory results were identified.…”