Life Sciences Commons^™

The Function Of Carmil1 In Migrating Cells, Marc Edwards

All Theses and Dissertations (ETDs)

This dissertation describes the physiological role of the Capping Protein- CARMIL interaction in migrating cells. I establish the CARMIL-CP complex as a key regulator of lamellipodial actin assembly and of lamellipodial dynamics. Membrane ruffling at the leading edge of motile cells and macropinocytosis were also found to be dependent on the CARMIL1-CP interaction. This is consistent with macropinocytosis and ruffling being dependent on a functional and dynamic lamellipodium.: Kerr and Teasdale, 2009).

In chapter two I demonstrate that the CBR of CARMIL1 is competent to inhibit CP in cells. I show that overexpression of the CBR in cells leads to …

An Expanded View Of The Eukaryotic Cytoskeleton, James B. Moseley

Dartmouth Scholarship

A rich and ongoing history of cell biology research has defined the major polymer systems of the eukaryotic cytoskeleton. Recent studies have identified additional proteins that form filamentous structures in cells and can self-assemble into linear polymers when purified. This suggests that the eukaryotic cytoskeleton is an even more complex system than previously considered. In this essay, I examine the case for an expanded definition of the eukaryotic cytoskeleton and present a series of challenges for future work in this area.

Shroom3 Deficient Mice Show Congenital Heart Defects, Rami R. Halabi

Electronic Thesis and Dissertation Repository

Congenital heart defects (CHDs) are associated with a number of genetic and environmental risk factors affecting approximately 1% of newborns. Shroom3 is an actin binding and microtubule organizing protein essential for neural tube closure in mouse, Xenopus and chick. In Xenopus shroom3 expression is found within the forming heart and loss of activity results in malformed hearts. In addition, SHROOM3 has recently been associated with heterotaxy in a human patient. Mice homozygous for the Shroom3 gene trap die at birth due to exencephaly and here, I provide evidence that the majority of these mice have CHDs, including septal defects, semilunar …

Identification Of Actin Cytoskeletal Protein Interactions With The Fission Yeast Scaffold, Mid1, Marian Testori

Masters Theses

Cancer is a disease of uncontrolled cell division. Cell division in eukaryotic cells occurs by the formation of a contractile ring, predominantly composed of filamentous actin (F-actin). During mitosis, actin filaments polymerize to form rings at the medial plane of the cell that constrict causing the cell membrane to pinch and divide. Proteins that regulate this process are essential because dysregulation can lead to uninhibited cell growth and division. In fission yeast, the protein Mid1 functions as a scaffold to recruit regulatory proteins required for actin filament formation and simultaneously anchors the contractile ring at the cell division site. The …

Susceptibility Of Apoptotic Cells To Hydrolysis By Spla2: Molecular Basis And Mechanisms Defined, Elizabeth Gibbons

Theses and Dissertations

Secretory phospholipase A2 hydrolyzes phospholipids at a lipid-water interface, resulting in pro-inflammatory products being released from cell membranes. Healthy cells are resistant to cleavage by this enzyme, but apoptotic cells become susceptible to its activity. Only bilayers with certain characteristics are able to be hydrolyzed. Most recently, studies in this lab have emphasized the idea that the biophysical state of the bilayer (in terms of lipid order, spacing, and fluidity) is relevant in determining the probability of one phospholipid escaping the membrane to be hydrolyzed. Prior to this study, it had been shown that apoptotic cells undergo biophysical alterations that …

Plant Cytoskeleton: Della Connects Gibberellins To Microtubules, Ram Dixit

Biology Faculty Publications & Presentations

A new study reveals that DELLA proteins directly interact with the prefoldin complex, thus regulating tubulin subunit availability in a gibberellin-dependent manner. This finding provides a mechanistic link between the growth-promoting plant hormone gibberellin and cortical microtubule organization.

Characterizing The Role Of Cortactin In Actin Pedestal Assembly By Enterohemorrhagic Escherichia Coli (Ehec), Sarah E. Grout

Honors Scholar Theses

Enterohemorrhagic Escherichia coli (EHEC) is a major foodborne cause of bloody diarrhea and renal failure. During colonization of the intestine, EHEC injects the transmembrane receptor protein Tir and the cytoplasmic effector protein EspFU into host cells to reorganize the actin cytoskeleton into adhesion “pedestals.” EspFU has been shown to bind and activate the actin nucleation factor N-WASP to drive actin polymerization into pedestals. However, EspFU can still assemble pedestals in cells lacking N-WASP, suggesting that this effector protein is able to also trigger N-WASP-independent pathways of actin polymerization during infection. Cortactin is an atypical nucleation factor that localizes to pedestals, …

Subcellular Analysis Of The Disulfide Proteome In P66shc Expressing Nerve Cells, Tyler Cann

Electronic Thesis and Dissertation Repository

The longevity associated protein p66Shc has been suggested to regulate organismal lifespan through initiation of apoptotic pathways. Following stress-induced translocation into the mitochondria, p66Shc promotes increased reactive oxygen species (ROS) production and triggers poorly defined downstream signaling events that lead to decreased cell viability. Protein disulfide bonding has recently emerged as aROSdependent post-translational modification that regulates protein function and signaling processes. Using the mouse hippocampal HT-22 cell line, I sought to determine the changes in the disulfide proteome associated with p66Shc mediatedROSproduction. Through Redox 2D-SDSPAGEanalysis of mitochondrial and cytosolic extracts, redox sensitive proteins altered by p66Shc mediatedROSformation were identified. Of …

Do Viruses Require The Cytoskeleton?, Jason D. Matthews, Rachel Morgan, Christie Sleigher, Teryl K. Frey

Biology Faculty Publications

Background: It is generally thought that viruses require the cytoskeleton during their replication cycle. However, recent experiments in our laboratory with rubella virus, a member of the family Togaviridae (genus rubivirus), revealed that replication proceeded in the presence of drugs that inhibit microtubules. This study was done to expand on this observation.
Findings: The replication of three diverse viruses, Sindbis virus (SINV; family Togaviridae family), vesicular stomatitis virus (VSV; family Rhabdoviridae), and Herpes simplex virus (family Herpesviridae), was quantified by the titer (plaque forming units/ml; pfu/ml) produced in cells treated with one of three anti-microtubule drugs (colchicine, noscapine, or paclitaxel) …