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Articles 1 - 7 of 7

Full-Text Articles in Cell Biology

Cargo Specific Regulation Of Cytoplasmic Dynein By Effector Proteins, Mara Olenick Jan 2018

Cargo Specific Regulation Of Cytoplasmic Dynein By Effector Proteins, Mara Olenick

Publicly Accessible Penn Dissertations

Axonal transport is vital for the development and survival of neurons. The transport of cargo and organelles from the axon to the cell body is driven almost completely by the molecular motor, cytoplasmic dynein. Yet, it remains unclear how dynein is spatially and temporally regulated given the variety of cargo that must be properly localized to maintain cellular function. Previous work has suggested that adaptor proteins provide a mechanism for cargo-specific regulation of motors. During my thesis work, I have investigated the role of mammalian Hook proteins, Hook1 and Hook3, as potential motor adaptors. Using optogenetic and single molecule assays ...


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 ...


Mechanochemical Control Of Stem Cell Biology In Development And Disease: Experimental And Theoretical Models, Polimyr Caesar Dave Pelisco Dingal Jan 2014

Mechanochemical Control Of Stem Cell Biology In Development And Disease: Experimental And Theoretical Models, Polimyr Caesar Dave Pelisco Dingal

Publicly Accessible Penn Dissertations

Whether a stem cell remains or egresses away from its physiological niche is a function of mechanical and soluble factors in a time-dependent manner, which implicates a `memory' of prior mechanochemical conditioning. Virtually every organ in the body contains resident stem or progenitor cells that contribute to organ homeostasis or repair. The wound healing process in higher vertebrate animals is spatiotemporally complex and usually leads to scarring. Limitations for the use of stem cells as regenerative therapy include the lack of expansion capabilities in vitro as well as materials issues that complicate traditional biochemical protocols. A minimal `scar in a ...


Local Cytoskeletal And Organelle Interactions Impact Molecular Motor-Driven Early Endosomal Trafficking, Allison Lorraine Zajac Jan 2013

Local Cytoskeletal And Organelle Interactions Impact Molecular Motor-Driven Early Endosomal Trafficking, Allison Lorraine Zajac

Publicly Accessible Penn Dissertations

Molecular motors generate the force needed for long-distance transport of cargos and organelles in the cell. How motor proteins attach to a diverse array of cargos and navigate to the correct location in the cell with enough fidelity to maintain organelle integrity is only starting to be understood. Studying the properties of individual motors, and their fine-tuning by regulatory molecules, is one area of active investigation in vitro. However, the organization of the cell, and the variability of the environment within a single cell, cannot be fully reconstituted in vitro. We investigated the effects of the crowded intracellular environment on ...


Cytoplasmic Dynein And Dynactin Coordinate Microtubule Dynamics At The Growing Plus End, Jacob Eric Lazarus Jan 2012

Cytoplasmic Dynein And Dynactin Coordinate Microtubule Dynamics At The Growing Plus End, Jacob Eric Lazarus

Publicly Accessible Penn Dissertations

Microtubules are cytoskeletal polymers that serve as long-distance tracks for intracellular transport. However, microtubules are not static tracks; they undergo dynamic instability, a non-equilibrium behavior which allows them to continually remodel. Microtubules must remodel to adapt to the changing needs of the cell, yet they must also be stable enough to allow long-distance transport by kinesins and by cytoplasmic dynein and its partner complex dynactin. Microtubule dynamics are strongly influenced by microtubule-associated proteins, which bind to microtubules and bias them toward growth or shrinkage. A pool of dynein and dynactin localizes to the microtubule plus end and to the cortex ...


Signaling By Non-Canonical Receptor Tyrosine Kinases Erbb3 And Ryk, Fumin Shi Jan 2012

Signaling By Non-Canonical Receptor Tyrosine Kinases Erbb3 And Ryk, Fumin Shi

Publicly Accessible Penn Dissertations

Signaling by receptor tyrosine kinases (RTKs) typically involves binding of extracellular ligands and subsequent activation of intracellular kinase domain, which in turn mediates autophosphorylation and downstream signal transduction. However, several RTKs, such as ErbB3 (HER3) and Ryk/Derailed, lack key conserved (and catalytically important) residues in their intracellular kinase domain, and are thought to be inactive `pseudo'-kinases. Much less is known regarding how these receptor tyrosine `pseudo'-kinases mediate transmembrane signaling. The work described in this dissertation attempts to understand the non-canonical signaling by ErbB3 and Ryk/Derailed using a combination of biophysical, biochemical and cell biology methods. ErbB3 ...