Enhanced Nucleocytoplasmic Transport Due to Competition for Elastic Binding Sites

Overview

Journal Biophys J

Publisher Cell Press

Specialty Biophysics

Date 2018 Jul 5

PMID 29972802

Citations 5

Authors

Ben Fogelson

James P Keener

Affiliations

Soon will be listed here.

Abstract

Nuclear pore complexes (NPCs) control all traffic into and out of the cell nucleus. NPCs are molecular machines that simultaneously achieve high selectivity and high transport rates. The biophysical details of how cargoes rapidly traverse the pore remain unclear but are known to be mediated by interactions between cargo-binding chaperone proteins and natively unstructured nucleoporin proteins containing many phenylalanine-glycine repeats (FG nups) that line the pore's central channel. Here, we propose a specific and detailed physical mechanism for the high speed of nuclear import based on the elasticity of FG nups and on competition between individual chaperone proteins for FG nup binding. We develop a mathematical model to support our proposed mechanism. We suggest that the recycling of nuclear import factors back to the cytoplasm is important for driving high-speed import and predict the existence of an optimal cytoplasmic concentration of cargo for enhancing the rate of import over a purely diffusive rate.

Citing Articles

Exploring Cellular Gateways: Unraveling the Secrets of Disordered Proteins within Live Nuclear Pores.

Yu W, Tingey M, Kelich J, Li Y, Yu J, Junod S Res Sq. 2024; .

PMID: 38260360 PMC: 10802689. DOI: 10.21203/rs.3.rs-3504130/v1.

Enhanced diffusion by reversible binding to active polymers.

Sridhar S, Dunagin J, Koo K, Hough L, Vernerey F Macromolecules. 2022; 54(4):1850-1858.

PMID: 35663922 PMC: 9161825. DOI: 10.1021/acs.macromol.0c02306.

Moving while you're stuck: a macroscopic demonstration of an active system inspired by binding-mediated transport in biology.

Koo K, Sridhar S, Clark N, Vernerey F, Hough L Soft Matter. 2021; 17(10):2957-2962.

PMID: 33595051 PMC: 9205265. DOI: 10.1039/d0sm01808b.

Bound-State Diffusion due to Binding to Flexible Polymers in a Selective Biofilter.

Maguire L, Betterton M, Hough L Biophys J. 2019; 118(2):376-385.

PMID: 31858976 PMC: 6976872. DOI: 10.1016/j.bpj.2019.11.026.

Design principles of selective transport through biopolymer barriers.

Maguire L, Stefferson M, Betterton M, Hough L Phys Rev E. 2019; 100(4-1):042414.

PMID: 31770897 PMC: 7502277. DOI: 10.1103/PhysRevE.100.042414.

References

Bickel T, Bruinsma R . The nuclear pore complex mystery and anomalous diffusion in reversible gels. Biophys J. 2002; 83(6):3079-87. PMC: 1302387. DOI: 10.1016/s0006-3495(02)75312-5. View

Kopito R, Elbaum M . Nucleocytoplasmic transport: a thermodynamic mechanism. HFSP J. 2009; 3(2):130-41. PMC: 2707793. DOI: 10.2976/1.3080807. View

Yang W, Gelles J, Musser S . Imaging of single-molecule translocation through nuclear pore complexes. Proc Natl Acad Sci U S A. 2004; 101(35):12887-92. PMC: 516490. DOI: 10.1073/pnas.0403675101. View

Raveh B, Karp J, Sparks S, Dutta K, Rout M, Sali A . Slide-and-exchange mechanism for rapid and selective transport through the nuclear pore complex. Proc Natl Acad Sci U S A. 2016; 113(18):E2489-97. PMC: 4983827. DOI: 10.1073/pnas.1522663113. View

Kim S, Elbaum M . Enzymatically driven transport: a kinetic theory for nuclear export. Biophys J. 2013; 105(9):1997-2005. PMC: 3835178. DOI: 10.1016/j.bpj.2013.09.011. View

Weis K, Dingwall C, Lamond A . Characterization of the nuclear protein import mechanism using Ran mutants with altered nucleotide binding specificities. EMBO J. 1996; 15(24):7120-8. PMC: 452537. View

Rout M, Aitchison J, Magnasco M, Chait B . Virtual gating and nuclear transport: the hole picture. Trends Cell Biol. 2003; 13(12):622-8. DOI: 10.1016/j.tcb.2003.10.007. View

Ando D, Zandi R, Kim Y, Colvin M, Rexach M, Gopinathan A . Nuclear pore complex protein sequences determine overall copolymer brush structure and function. Biophys J. 2014; 106(9):1997-2007. PMC: 4017316. DOI: 10.1016/j.bpj.2014.03.021. View

Ribbeck K, Gorlich D . Kinetic analysis of translocation through nuclear pore complexes. EMBO J. 2001; 20(6):1320-30. PMC: 145537. DOI: 10.1093/emboj/20.6.1320. View

10.

Ando D, Gopinathan A . Cooperative Interactions between Different Classes of Disordered Proteins Play a Functional Role in the Nuclear Pore Complex of Baker's Yeast. PLoS One. 2017; 12(1):e0169455. PMC: 5222603. DOI: 10.1371/journal.pone.0169455. View

11.

Hough L, Dutta K, Sparks S, Temel D, Kamal A, Tetenbaum-Novatt J . The molecular mechanism of nuclear transport revealed by atomic-scale measurements. Elife. 2015; 4. PMC: 4621360. DOI: 10.7554/eLife.10027. View

12.

Schmidt H, Gorlich D . Transport Selectivity of Nuclear Pores, Phase Separation, and Membraneless Organelles. Trends Biochem Sci. 2015; 41(1):46-61. DOI: 10.1016/j.tibs.2015.11.001. View

13.

Denning D, Patel S, Uversky V, Fink A, Rexach M . Disorder in the nuclear pore complex: the FG repeat regions of nucleoporins are natively unfolded. Proc Natl Acad Sci U S A. 2003; 100(5):2450-5. PMC: 151361. DOI: 10.1073/pnas.0437902100. View

14.

Yang W, Musser S . Nuclear import time and transport efficiency depend on importin beta concentration. J Cell Biol. 2006; 174(7):951-61. PMC: 2064387. DOI: 10.1083/jcb.200605053. View

15.

Zilman A, Di Talia S, Chait B, Rout M, Magnasco M . Efficiency, selectivity, and robustness of nucleocytoplasmic transport. PLoS Comput Biol. 2007; 3(7):e125. PMC: 1914370. DOI: 10.1371/journal.pcbi.0030125. View

16.

Meyer R, Obermayer K . pypet: A Python Toolkit for Data Management of Parameter Explorations. Front Neuroinform. 2016; 10:38. PMC: 4996826. DOI: 10.3389/fninf.2016.00038. View

17.

Peters R . Translocation through the nuclear pore complex: selectivity and speed by reduction-of-dimensionality. Traffic. 2005; 6(5):421-7. DOI: 10.1111/j.1600-0854.2005.00287.x. View

18.

Lim R, Huang N, Koser J, Deng J, Lau K, Schwarz-Herion K . Flexible phenylalanine-glycine nucleoporins as entropic barriers to nucleocytoplasmic transport. Proc Natl Acad Sci U S A. 2006; 103(25):9512-7. PMC: 1480438. DOI: 10.1073/pnas.0603521103. View

19.

Strambio-De-Castillia C, Niepel M, Rout M . The nuclear pore complex: bridging nuclear transport and gene regulation. Nat Rev Mol Cell Biol. 2010; 11(7):490-501. DOI: 10.1038/nrm2928. View

20.

Krishnan V, Lau E, Yamada J, Denning D, Patel S, Colvin M . Intramolecular cohesion of coils mediated by phenylalanine--glycine motifs in the natively unfolded domain of a nucleoporin. PLoS Comput Biol. 2008; 4(8):e1000145. PMC: 2475668. DOI: 10.1371/journal.pcbi.1000145. View