BCH3021 Lecture Notes - Lecture 13: Replication Protein A, Rcc1, Nuclear Transport
Lecture 13 – Nuclear Import and Export
Getting Molecules into the Nucleus
• Transport of RanGDP is NTF2
• RanGDP (cytoplasm) → RanGTP (nucleus)
o Converted by RCC1
• Maintenance of nuclear RanGTP
o RanGAP (Ran GTPase activating protein) catalyzes GTP hydrolysis in
association with RanBP1 (Ran binding protein 1) in cytoplasm
o Gradient of high nuclear RanGTP and low cytoplasmic RanGTP
needed for nucleocytoplasmic transport is achieved by:
▪ Transport of Ran (RanGDP) into nucleus by NTF2
▪ Compartmentalisation of RCC1 (nucleus) and RanGAP1
(cytoplasm) to ensure nuclear Ran is converted to GTP bound
form
o Ran gradient determines directionality of nuclear transport
o Don’t want RanGTP to build up in cytoplasm because it will inhibit
import
o Need RanGTP in high amount for export
• IMP α funcations as adaptor for linking NLS containing protein to IMPβ
• IMPβ doesn’t bind it directly – needs IMP α but does need OTHER adaptors
Other Ran-Dependent Nuclear Import Pathawys
• Pathways that use adaptors other than IMPα
o Snurportin – contains an IBB domain
▪ Mediates nuclear import of snRNPs and mediates transport into
the nucleus as a heterodimer with importin β1
o XRIP α
▪ Mediates nuclear import of single stranded DNA binding to
replication protein A (RPA) → mediates transport into the
nucleus as a heterodimer with importin β1
• IMPβ-homologue nuclear import pathways
o NLS dependent nuclear transport pathways – no adaptor is required
▪ IMPβ homologue performs the role of:
• IMPα in terms of NLS recognition
• IMPβ (=IMPβ1) in terms of NPC docking through
binding to nups and substrate release within nucleus
through binding to RanGTP
o Other IMPβ (24 in higher eukaryotes) mediate nuclear import and
export of specific classes of proteins (provide examples in exam)
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Imp funcations as adaptor for linking nls containing protein to imp . Imp doesn"t bind it directly needs imp but does need other adaptors. Imp -homologue nuclear import pathways: nls dependent nuclear transport pathways no adaptor is required. , e. g. basic leucine zipper tfs (ap1-jun/fos: imp 2 (transportin) Import of mrna binding proteins (hnrnps) containing largely hydrophobic nls, m9. Import of ribosomal proteins and certain transcriptional factors: imp 1, imp 3, imp 4. Protein export from the nucleus ran-dependent nuclear transport pathways. Imp 1 recycled back to cytoplasm in a complex with. Rangtp: specific exportins mediate nuclear export of particular proteins, exportin 4 mediates nuclear export of eif-5a and tf smad3, exportin 5 (msn5/kap142) mediates nuclear export of the tf. Pho4, mig1 glucose reporessor and dsrna proteins: exportin 7 mediates nuclear export of signalling molecules. Rangtp: larger molecules more complex, more adaptors and mediators different for both, mrna export, couple to splicing, multiple factors involved: incl.
