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Articles 1 - 5 of 5

Full-Text Articles in Molecular Biology

Engineered Cytoskeletal Arrays Reveal Mechanisms Of Membrane Transport And Tubulation, Betsy Buechler Mcintosh Jan 2017

Engineered Cytoskeletal Arrays Reveal Mechanisms Of Membrane Transport And Tubulation, Betsy Buechler Mcintosh

Publicly Accessible Penn Dissertations

Within the cell, cytoskeletal molecular motors transport and remodel membrane-bound cargos along microtubule and actin filament tracks. Typically, there are multiple actin and microtubule motors attached to the same cargo, which must coordinate to navigate a complex cytoskeletal environment and deliver their cargos to specific locations. We used an engineering, in vitro reconstitution, approach to investigate the interplay between a processive, microtubule-based motor, kinesin-1, and a non-processive, actin filament-based motor, Myo1c, in a simplified environment with increasing physiological complexity. First, we examined the interplay between purified motors attached to a membrane-coated bead at individual actin filament/microtubule intersections on the ...


Molecular And Cellular Approaches Toward Understanding Dynein-Driven Motility, Swathi Ayloo Jan 2016

Molecular And Cellular Approaches Toward Understanding Dynein-Driven Motility, Swathi Ayloo

Publicly Accessible Penn Dissertations

Active transport is integral to organelle localization and their distribution within the cell. Kinesins, myosins and dynein are the molecular motors that drive this long range transport on the actin and microtubule cytoskeleton. Although several families of kinesins and myosins have evolved, there is only one form of cytoplasmic dynein driving active retrograde transport in cells. While dynactin is an essential co-factor for most cellular functions of dynein, the mechanistic basis for this evolutionarily well conserved interaction remains unclear. Here, I use single molecule approaches with purified dynein to reconstitute processes in vitro, and implement an optogenetic tool in neurons ...


The Regulation Of Psf Activity In T Cells By Trap150 And Gsk3, Christopher Yarosh Jan 2016

The Regulation Of Psf Activity In T Cells By Trap150 And Gsk3, Christopher Yarosh

Publicly Accessible Penn Dissertations

PSF is a ubiquitously expressed and essential nuclear protein that influences many aspects of the genome maintenance and gene expression pathways. Although previous studies have identified numerous protein cofactors and nucleic acid targets of PSF, insufficient work has been done to understand how it is regulated to accomplish its various functions in a coordinated manner. Previous research in the Lynch laboratory demonstrated that, in T cells, PSF is a downstream target of the serine/threonine kinase GSK3. Phosphorylation of PSF T687 by GSK3 promotes interaction of PSF with another multifunctional nuclear factor, TRAP150. This interaction prevents PSF from binding RNA ...


The Molecular Basis Of Substrate Recognition By The Family Of Pellino E3 Ubiquitin Ligases, Yu-San Huoh Jan 2013

The Molecular Basis Of Substrate Recognition By The Family Of Pellino E3 Ubiquitin Ligases, Yu-San Huoh

Publicly Accessible Penn Dissertations

The four mammalian Pellinos (Pellinos 1, 2, 3a, and 3b) are E3 ubiquitin ligases that have emerging roles in the regulation of Toll-like receptors, interleukin-1 receptor, T-cell receptor, Nod2, and TNF receptor signaling pathways. While each Pellino has a distinct role in facilitating various cellular processes, the underlying mechanisms by which these highly homologous proteins act selectively in these signaling pathways are not clear. In this dissertation, we elucidate the molecular basis of Pellino substrate specificity in order to gain a better understanding of the roles that individual Pellinos play in orchestrating inflammation and cell death. Pellino substrate recognition is ...


Phoq: Structural And Mechanistic Investigations Into An Important Bacterial Sensor Kinase, Graham David Clinthorne Jan 2012

Phoq: Structural And Mechanistic Investigations Into An Important Bacterial Sensor Kinase, Graham David Clinthorne

Publicly Accessible Penn Dissertations

Two-component systems represent the dominant mechanism for cellular signal transduction in prokaryotes. One particular system, PhoQ, has been the focus of our interest because it is the switch that controls virulence in Salmonella and other pathogenic gram negative bacteria. Certain domains of PhoQ and other two-component systems have been studied extensively and this research has yielded several structures with atomic level resolution. However, no complete structure or experimentally-based model has been forthcoming and the precise mechanism by which these diverse systems transmit signals from the exterior of the cell to the interior has remained elusive. We have undertaken a study ...