Chromatin; Chromosomes; Nuclear Envelope; Nuclear Pore; Nuclear Pore Complex Proteins
Discovery to Cure Internship
The Lusk lab focuses on understanding the molecular mechanisms that control the organization, structure and function of the nuclear envelope: the membrane system that encapsulates the genome of all eukaryotes.
At the heart of this pursuit is the examination of the function of membrane proteins that selectively enrich at the nuclear envelope. Mutation or deletion of several genes encoding these proteins have profound effects on cellular processes that result in the loss of nuclear envelope structure along with changes in gene expression and an increase in genome instability. These phenotypes often lead to cell death or the manifestation of specific diseases termed nuclear envelopathies. To fully understand the mechanisms that contribute to these essential processes, we have identified conserved integral membrane proteins in the budding yeast S. cerevisiae. Using yeast as a model system allows us to use a myriad of genetic, biochemical and cell biological methodology to directly examine how membrane proteins affect various aspects of nuclear envelope physiology. Ongoing projects in the lab include (a) defining mechanisms of nuclear pore complex assembly and distribution (b) understanding membrane protein traffic to the inner nuclear membrane (c) investigating the role of membrane proteins in controlling transcription, gene recruitment and genome stability at the nuclear periphery.
Specialized Terms: Nuclear pore complex; Nuclear periphery; Membrane proteins; Chromatin structure
Surveillance of nuclear pore complex assembly by ESCRT-III/Vps4.
Webster, BM, Colombi, P, Jager, J, Lusk, CP. Surveillance of nuclear pore complex assembly by ESCRT-III/Vps4. Cell. 2014. 159(2): 388-401
The transmission of nuclear pore complexes to daughter cells requires a cytoplasmic pool of Nsp1.
Colombi, P, Webster, BM, Frohlich, F, Lusk, C.P. The transmission of nuclear pore complexes to daughter cells requires a cytoplasmic pool of Nsp1. Journal of Cell Biology. 2013. 203(2)
Lumenal interactions in nuclear pore complex assembly and stability.
Yewdell, W.T., Colombi, P, Makhnevych, T., Lusk C.P. Lumenal interactions in nuclear pore complex assembly and stability. Molecular Biology of the Cell. 2011. 22(8):1375-88
Highway to the inner nuclear membrane: rules for the road.
Lusk, C.P., Blobel, G., King M.C. Highway to the inner nuclear membrane: rules for the road. Nature Reviews Molecular and Cellular Biology. 2007, 8: 414-420.
Karyopherin-mediated import of integral inner nuclear membrane proteins.
King, M.C.*, Lusk C.P.*, G. Blobel. Karyopherin-mediated import of integral inner nuclear membrane proteins. Nature. 2006, 442: 1003-7 * equal contributions
Karyopherins in nuclear pore biogenesis: a role for Kap121p in the assembly of Nup53p into nuclear pore complexes.
Lusk, C.P., T. Makhnevych, M. Marelli, J.D. Aitchison, R.W. Wozniak. Karyopherins in nuclear pore biogenesis: a role for Kap121p in the assembly of Nup53p into nuclear pore complexes. Journal of Cell Biology. 2002, 159: 267-278.
Full List of PubMed Publications
- Fisher PDE, Shen Q, Akpinar B, Davis LK, Chung KKH, Baddeley D, Šarić A, Melia TJ, Hoogenboom BW, Lin C, Lusk CP: A Programmable DNA Origami Platform for Organizing Intrinsically Disordered Nucleoporins within Nanopore Confinement. ACS Nano. 2018 Jan 25; 2018 Jan 25. PMID: 29350911
- Lusk CP, King MC: The nucleus: keeping it together by keeping it apart. Curr Opin Cell Biol. 2017 Feb; 2017 Feb 23. PMID: 28236735
- Webster BM, Thaller DJ, Jäger J, Ochmann SE, Borah S, Lusk CP: Chm7 and Heh1 collaborate to link nuclear pore complex quality control with nuclear envelope sealing. EMBO J. 2016 Nov 15; 2016 Oct 12. PMID: 27733427
- Del Viso F, Huang F, Myers J, Chalfant M, Zhang Y, Reza N, Bewersdorf J, Lusk CP, Khokha MK: Congenital Heart Disease Genetics Uncovers Context-Dependent Organization and Function of Nucleoporins at Cilia. Dev Cell. 2016 Sep 12; 2016 Sep 1. PMID: 27593162
- Huang F, Sirinakis G, Allgeyer ES, Schroeder LK, Duim WC, Kromann EB, Phan T, Rivera-Molina FE, Myers JR, Irnov I, Lessard M, Zhang Y, Handel MA, Jacobs-Wagner C, Lusk CP, Rothman JE, Toomre D, Booth MJ, Bewersdorf J: Ultra-High Resolution 3D Imaging of Whole Cells. Cell. 2016 Aug 11; 2016 Jul 7. PMID: 27397506
- King MC, Lusk CP: A model for coordinating nuclear mechanics and membrane remodeling to support nuclear integrity. Curr Opin Cell Biol. 2016 Aug; 2016 Mar 28. PMID: 27031045
- Lusk CP: Baby Nuclear Pores Grow Up Faster All the Time. Cell. 2016 Jul 28. PMID: 27471962
- Webster BM, Lusk CP: Border Safety: Quality Control at the Nuclear Envelope. Trends Cell Biol. 2016 Jan; 2015 Oct 1. PMID: 26437591
- Webster BM, Lusk CP: ESCRTs breach the nuclear border. Nucleus. 2015; 2015 May 5. PMID: 25942571
- Webster BM, Colombi P, Jäger J, Lusk CP: Surveillance of nuclear pore complex assembly by ESCRT-III/Vps4. Cell. 2014 Oct 9. PMID: 25303532
- Lusk CP, Colombi P: Toward a consensus on the mechanism of nuclear pore complex inheritance. Nucleus. 2014 Mar-Apr; 2014 Feb 25. PMID: 24637838
- Colombi P, Webster BM, Fröhlich F, Lusk CP: The transmission of nuclear pore complexes to daughter cells requires a cytoplasmic pool of Nsp1. J Cell Biol. 2013 Oct 28. PMID: 24165936
- Meinema AC, Laba JK, Hapsari RA, Otten R, Mulder FA, Kralt A, van den Bogaart G, Lusk CP, Poolman B, Veenhoff LM: Long unfolded linkers facilitate membrane protein import through the nuclear pore complex. Science. 2011 Jul 1; 2011 Jun 9. PMID: 21659568
- Yewdell WT, Colombi P, Makhnevych T, Lusk CP: Lumenal interactions in nuclear pore complex assembly and stability. Mol Biol Cell. 2011 Apr 15; 2011 Feb 23. PMID: 21346187
- Highsmith MJ, Carey SL, Koelsch KW, Lusk CP, Maitland ME: Design and fabrication of a passive-function, cylindrical grasp terminal device. Prosthet Orthot Int. 2009 Dec. PMID: 19961298
- Ramirez IA, Lusk CP, Dubey R, Highsmith MJ, Maitland ME: Crossed four-bar mechanism for improved prosthetic grasp. J Rehabil Res Dev. 2009. PMID: 20157858
- Lusk CP, Waller DD, Makhnevych T, Dienemann A, Whiteway M, Thomas DY, Wozniak RW: Nup53p is a target of two mitotic kinases, Cdk1p and Hrr25p. Traffic. 2007 Jun; 2007 Apr 25. PMID: 17461799
- Lusk CP, Blobel G, King MC: Highway to the inner nuclear membrane: rules for the road. Nat Rev Mol Cell Biol. 2007 May; 2007 Apr 18. PMID: 17440484
- Makhnevych T, Ptak C, Lusk CP, Aitchison JD, Wozniak RW: The role of karyopherins in the regulated sumoylation of septins. J Cell Biol. 2007 Apr 9; 2007 Apr 2. PMID: 17403926
- King MC, Lusk CP, Blobel G: Karyopherin-mediated import of integral inner nuclear membrane proteins. Nature. 2006 Aug 31; 2006 Aug 23. PMID: 16929305
- Scott RJ, Lusk CP, Dilworth DJ, Aitchison JD, Wozniak RW: Interactions between Mad1p and the nuclear transport machinery in the yeast Saccharomyces cerevisiae. Mol Biol Cell. 2005 Sep; 2005 Jul 6. PMID: 16000377
- Lusk CP, Makhnevych T, Wozniak RW: New ways to skin a kap: mechanisms for controlling nuclear transport. Biochem Cell Biol. 2004 Dec. PMID: 15674429
- Makhnevych T, Lusk CP, Anderson AM, Aitchison JD, Wozniak RW: Cell cycle regulated transport controlled by alterations in the nuclear pore complex. Cell. 2003 Dec 26. PMID: 14697200
- Wozniak RW, Lusk CP: Nuclear pore complexes. Curr Biol. 2003 Mar 4. PMID: 12620203
- Lusk CP, Makhnevych T, Marelli M, Aitchison JD, Wozniak RW: Karyopherins in nuclear pore biogenesis: a role for Kap121p in the assembly of Nup53p into nuclear pore complexes. J Cell Biol. 2002 Oct 28; 2002 Oct 28. PMID: 12403813
- Marelli M, Lusk CP, Chan H, Aitchison JD, Wozniak RW: A link between the synthesis of nucleoporins and the biogenesis of the nuclear envelope. J Cell Biol. 2001 May 14. PMID: 11352933