C. Patrick Lusk
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View article: Detecting Nuclear Pore Complex assembly in living cells
Detecting Nuclear Pore Complex assembly in living cells Open
The formation of nuclear pore complexes (NPCs) - vital gateways regulating nuclear-cytoplasmic transport - is a highly orchestrated process requiring the integration of hundreds of nucleoporins into the nuclear envelope. A major challenge …
View article: A yeast model reveals the SMAD3 nuclear import mechanism
A yeast model reveals the SMAD3 nuclear import mechanism Open
TGF-β signaling is important for patterning tissues during embryonic development and relies on the nuclear import of SMADs. Basal SMAD nuclear import mechanisms remain to be fully understood and could benefit from advances in our understan…
View article: The LINC complex component Kms1 and CENP-B protein Cbp1 cooperate to enforce faithful homology-directed DNA repair at the nuclear periphery in <i>S. pombe</i>
The LINC complex component Kms1 and CENP-B protein Cbp1 cooperate to enforce faithful homology-directed DNA repair at the nuclear periphery in <i>S. pombe</i> Open
While homologous recombination (HR) is often considered to be an error-free DNA repair mechanism, the fidelity of this pathway depends on the cell’s ability to engage the ideal template, the replicated sister chromatid. This is particularl…
View article: Nup107 contributes to the maternal-to-zygotic transition by preventing the premature nuclear export of pri-miR427
Nup107 contributes to the maternal-to-zygotic transition by preventing the premature nuclear export of pri-miR427 Open
Emerging evidence suggests that the nuclear pore complex can have unique compositions and distinct nucleoporin functions in different cells. Here, we show that Nup107, a key component of the NPC scaffold, varies in expression over developm…
View article: Channel width modulates the permeability of DNA origami–based nuclear pore mimics
Channel width modulates the permeability of DNA origami–based nuclear pore mimics Open
Nucleoporins (nups) in the nuclear pore complex (NPC) form a selective barrier that suppresses the diffusion of most macromolecules while enabling rapid transport of nuclear transport receptor (NTR)–bound cargos. Recent studies have shown …
View article: Visualizing nuclear pore complex plasticity with pan-Expansion Microscopy
Visualizing nuclear pore complex plasticity with pan-Expansion Microscopy Open
The exploration of cell-type and environmentally-responsive nuclear pore complex (NPC) plasticity requires new, accessible tools. Using pan-Expansion Microscopy (pan-ExM), NPCs were identified by machine learning-facilitated segmentation w…
View article: Channel width modulates the permeability of DNA origami based nuclear pore mimics
Channel width modulates the permeability of DNA origami based nuclear pore mimics Open
Nucleoporins (nups) in the central channel of nuclear pore complexes (NPCs) form a selective barrier that suppresses the diffusion of most macromolecules while enabling rapid transport of nuclear transport receptors (NTRs) with bound cargo…
View article: A quantitative ultrastructural timeline of nuclear autophagy reveals a role for dynamin-like protein 1 at the nuclear envelope
A quantitative ultrastructural timeline of nuclear autophagy reveals a role for dynamin-like protein 1 at the nuclear envelope Open
Autophagic mechanisms that maintain nuclear envelope homeostasis are bulwarks to aging and disease. By leveraging 4D lattice light sheet microscopy and correlative light and electron tomography, we define a quantitative and ultrastructural…
View article: Changing the guard—nuclear pore complex quality control
Changing the guard—nuclear pore complex quality control Open
The integrity of the nuclear envelope depends on the function of nuclear pore complexes (NPCs), transport channels that control macromolecular traffic between the nucleus and cytosol. The central importance of NPCs suggests the existence o…
View article: The capsid lattice engages a bipartite NUP153 motif to mediate nuclear entry of HIV-1 cores
The capsid lattice engages a bipartite NUP153 motif to mediate nuclear entry of HIV-1 cores Open
Increasing evidence has suggested that the HIV-1 capsid enters the nucleus in a largely assembled, intact form. However, not much is known about how the cone-shaped capsid interacts with the nucleoporins (NUPs) in the nuclear pore for cros…
View article: Functionalized DNA-Origami-Protein Nanopores Generate Large Transmembrane Channels with Programmable Size-Selectivity
Functionalized DNA-Origami-Protein Nanopores Generate Large Transmembrane Channels with Programmable Size-Selectivity Open
The DNA-origami technique has enabled the engineering of transmembrane nanopores with programmable size and functionality, showing promise in building biosensors and synthetic cells. However, it remains challenging to build large (>10 nm),…
View article: An ESCRT grommet cooperates with a diffusion barrier to maintain nuclear integrity
An ESCRT grommet cooperates with a diffusion barrier to maintain nuclear integrity Open
The molecular mechanisms by which the endosomal sorting complexes required for transport (ESCRT) proteins contribute to the integrity of the nuclear envelope (NE) barrier are not fully defined. Here, we leveraged the single NE hole generat…
View article: Kap-β2/Transportin mediates β-catenin nuclear transport in Wnt signaling
Kap-β2/Transportin mediates β-catenin nuclear transport in Wnt signaling Open
Wnt signaling is essential for many aspects of embryonic development including the formation of the primary embryonic axis. In addition, excessive Wnt signaling drives multiple diseases including cancer, highlighting its importance for dis…
View article: Quality control mechanisms that protect nuclear envelope identity and function
Quality control mechanisms that protect nuclear envelope identity and function Open
The nuclear envelope (NE) is a specialization of the endoplasmic reticulum with distinct biochemistry that defines inner and outer membranes connected at a pore membrane that houses nuclear pore complexes (NPCs). Quality control mechanisms…
View article: Emerging Connections between Nuclear Pore Complex Homeostasis and ALS
Emerging Connections between Nuclear Pore Complex Homeostasis and ALS Open
Developing effective treatments for neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) requires understanding of the underlying pathomechanisms that contribute to the motor neuron loss that defines the disease. As it ca…
View article: Atg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosome
Atg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosome Open
Mechanisms that turn over components of the nucleus and inner nuclear membrane (INM) remain to be fully defined. We explore how components of the INM are selected by a cytosolic autophagy apparatus through a transmembrane nuclear envelope–…
View article: DNA-Origami NanoTrap for Studying the Selective Barriers Formed by Phenylalanine-Glycine-Rich Nucleoporins
DNA-Origami NanoTrap for Studying the Selective Barriers Formed by Phenylalanine-Glycine-Rich Nucleoporins Open
DNA nanotechnology provides a versatile and powerful tool to dissect the structure-function relationship of biomolecular machines like the nuclear pore complex (NPC), an enormous protein assembly that controls molecular traffic between the…
View article: Nuclear accumulation of CHMP7 initiates nuclear pore complex injury and subsequent TDP-43 dysfunction in sporadic and familial ALS
Nuclear accumulation of CHMP7 initiates nuclear pore complex injury and subsequent TDP-43 dysfunction in sporadic and familial ALS Open
Nuclear accumulation of CHMP7 leads to multiple cellular pathologies that can be mitigated via CHMP7 ASOs in familial and sporadic ALS iPSNs.
View article: Kap-β2/Transportin mediates β-catenin nuclear transport in Wnt signaling
Kap-β2/Transportin mediates β-catenin nuclear transport in Wnt signaling Open
SUMMARY Wnt signaling is essential for many aspects of embryonic development including the formation of the primary embryonic axis. In addition, excessive Wnt signaling drives multiple diseases including cancer highlighting its importance …
View article: Heh2/Man1 may be an evolutionarily conserved sensor of NPC assembly state
Heh2/Man1 may be an evolutionarily conserved sensor of NPC assembly state Open
It remains unknown whether there are mechanisms that can recognize defective NPCs. Biochemical and genetic analyses of the interactions between Heh2 and NPCs suggest that Heh2 may be a sensor of the NPC assembly state.
View article: Atg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosome
Atg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosome Open
Mechanisms that turnover components of the nucleus and inner nuclear membrane (INM) remain to be fully defined. We explore how components of the INM are selected by a cytosolic autophagy apparatus through a transmembrane nuclear envelope-l…
View article: A DNA-origami NanoTrap for studying the diffusion barriers formed by Phe-Gly-rich nucleoporins
A DNA-origami NanoTrap for studying the diffusion barriers formed by Phe-Gly-rich nucleoporins Open
SUMMARY DNA nanotechnology provides a versatile and powerful tool to dissect the structure-function relationship of biomolecular machines like the nuclear pore complex (NPC), an enormous protein assembly that controls molecular traffic bet…
View article: Direct binding of ESCRT protein Chm7 to phosphatidic acid–rich membranes at nuclear envelope herniations
Direct binding of ESCRT protein Chm7 to phosphatidic acid–rich membranes at nuclear envelope herniations Open
Mechanisms that control nuclear membrane remodeling are essential to maintain the integrity of the nucleus but remain to be fully defined. Here, we identify a phosphatidic acid (PA)–binding capacity in the nuclear envelope (NE)–specific ES…
View article: A physicochemical perspective of aging from single-cell analysis of pH, macromolecular and organellar crowding in yeast
A physicochemical perspective of aging from single-cell analysis of pH, macromolecular and organellar crowding in yeast Open
Cellular aging is a multifactorial process that is characterized by a decline in homeostatic capacity, best described at the molecular level. Physicochemical properties such as pH and macromolecular crowding are essential to all molecular …