Table 1 Summary of the NTR family members and their NLS-dependent and -independent chaperone activity
From: Nuclear-import receptors as gatekeepers of pathological phase transitions in ALS/FTD
NTR | Synonyms | Full name | Reported chaperone and/or disaggregase activity |
|---|---|---|---|
Karyopherin-α family: α-importins | |||
  KPNA1 | NPI-1, RCH2 | Importin-α5 |  |
  KPNA2 | RCH1 | Importin-α1 | • Disrupt oligomerization of TDP-43 N-terminal domain [38] • Prevent nuclear SENP2 association with cytoplasmic membranes [39] |
  KPNA3 | QIP2 | Importin-α4 |  |
  KPNA4 | QIP-1 | Importin-α3 |  |
  KPNA5 |  | Importin-α6 |  |
  KPNA6 |  | Importin-α7 |  |
  KPNA7 |  | Importin-α8 |  |
Karyopherin-β family: β-importins, exportins, biportins | |||
 β-importins | |||
  KPNB1 | IPO1, Kapβ1, NTF97 | Karyopherin-β1, Importin-β1 | • Chaperone and disaggregate TDP-43: via its classical NLS in concert with importin-α [38, 40, 41], and its PrLD in concert with FG-Nups [42] • Chaperone and disaggregate FUS via its RGG regions [43, 44] • Suppress poly(GR) condensation in vitro [41] • Reduce cytoplasmic aggregation of FG-Nups: Nup62 [42], Nup107, Nup153 and yeast Nup49 [45, 46] • Suppress in vitro aggregation of basic proteins: rpL4, rpL6 and histone H1 (together with IPO7), rpL18a [47] |
  TNPO1 | IPO2, Kapβ2, KPNB2, TRN, MIP1 | Transportin-1, Karyopherin-β2 | • Chaperone and disaggregate FUS: via its PY-NLS [40, 48,49,50,51,52,53,54] and its RGG regions [43, 44] • Chaperone and disaggregate other RBPs with a PY-NLS: TAF15, EWSR1, hnRNPA1 and hnRNPA2 [40] • Suppress poly(GR) condensation in vitro [41] • Prevent nucleoporin Nup153 association with cytoplasmic membranes [55] • Suppress phase separation of CIRBP via its RG/RGG region [56] |
  TNPO2 | IPO3, KPNB2B | Transportin-2, Karyopherin-β2b | • Reduce cytoplasmic TDP-CTF aggregation [42] |
  TNPO3 | IPO12, TRN-SR | Transportin-3, Transportin-SR | • Reduce cytoplasmic TDP-CTF aggregation [42] • Chaperone and disaggregate FUS via its RGG regions [43, 44] • Suppress phase separation of CIRBP via its RSY region [56] |
  IPO4 | RanBP4 | Importin-4 | • Reduce cytoplasmic TDP-CTF aggregation [42] • Prevent cytoplasmic accumulation of yeast nucleoporin Pom33 [57] • Chaperone histone complex H3-H4-ASF1 [58] • Suppress in vitro aggregation of basic ribosomal protein rpS3a [47] |
  IPO5 | KPNB3, Kapβ3, RanBP5 | Importin-5 | • Suppress in vitro aggregation of basic ribosomal protein rpL23a [47] |
  IPO7 | RanBP7 | Importin7 | • Chaperone and disaggregate FUS via its RGG regions [43, 44] • Suppress in vitro aggregation of basic proteins: rpL4, rpL6 and histone H1 (together with IPO7), rpL23a [47] |
  IPO8 | RanBP8 | Importin-8 |  |
  IPO9 | RanBP9 | Importin-9 | • Reduce cytoplasmic TDP-CTF aggregation [42] • Chaperone histone complex H2A-H2B [59] • Suppress in vitro aggregation of basic ribosomal proteins: rpL18a, rpS7 [47] |
  IPO11 | RanBP11 | Importin-11 |  |
 Exportins | |||
  XPO1 | CRM1 | Exportin-1 | • Reduce formation of cytoplasmic FG-Nup condensates [60] |
  XPO2 | CAS, CSE1L | Exportin-2 |  |
  XPOT | XPO3 | Exportin-t |  |
  XPO5 | RanBP21 | Exportin-5 |  |
  XPO6 | RanBP20 | Exportin-6 |  |
 Biportins |  |  | |
  IPO13 | RanBP13 | Importin-13 | • Reduce cytoplasmic aggregation of TDP-CTF and Nup62 [42] • Prevent Ubc9 from interacting with its cytoplasmic partners during nuclear import [61] |
  XPO4 |  | Exportin-4 | • Prevent nucleolar aggregation of cytoplasmic eIF5A [62] |
  XPO7 | RanBP16 | Exportin-7 |  |
 Unknown transport function | |||
  RanBP6 |  | Ran-binding protein 6 |  |
  RanBP17 |  | Ran-binding protein 17 |  |