Browsing by Subject "Eukaryotic Cells"

Now showing 1 - 2 of 2

Open Access
Bimodal analysis reveals a general scaling law governing nondirected and chemotactic cell motility.
(Biophysical journal, 2010-07) Gruver, J Scott; Potdar, Alka A; Jeon, Junhwan; Sai, Jiqing; Anderson, Bridget; Webb, Donna; Richmond, Ann; Quaranta, Vito; Cummings, Peter T; Chung, Chang Y
Cell motility is a fundamental process with relevance to embryonic development, immune response, and metastasis. Cells move either spontaneously, in a nondirected fashion, or in response to chemotactic signals, in a directed fashion. Even though they are often studied separately, both forms of motility share many complex processes at the molecular and subcellular scale, e.g., orchestrated cytoskeletal rearrangements and polarization. In addition, at the cellular level both types of motility include persistent runs interspersed with reorientation pauses. Because there is a great range of variability in motility among different cell types, a key challenge in the field is to integrate these multiscale processes into a coherent framework. We analyzed the motility of Dictyostelium cells with bimodal analysis, a method that compares time spent in persistent versus reorientation mode. Unexpectedly, we found that reorientation time is coupled with persistent time in an inverse correlation and, surprisingly, the inverse correlation holds for both nondirected and chemotactic motility, so that the full range of Dictyostelium motility can be described by a single scaling relationship. Additionally, we found an identical scaling relationship for three human cell lines, indicating that the coupling of reorientation and persistence holds across species and making it possible to describe the complexity of cell motility in a surprisingly general and simple manner. With this new perspective, we analyzed the motility of Dictyostelium mutants, and found four in which the coupling between two modes was altered. Our results point to a fundamental underlying principle, described by a simple scaling law, unifying mechanisms of eukaryotic cell motility at several scales.
Open Access
Targeting phosphorylation of eukaryotic initiation factor-2α to treat human disease.
(Progress in molecular biology and translational science, 2012-01) Fullwood, Melissa J; Zhou, Wei; Shenolikar, Shirish
The unfolded protein response, also known as endoplasmic reticulum (ER) stress, has been implicated in numerous human diseases, including atherosclerosis, cancer, diabetes, and neurodegenerative disorders. Protein misfolding activates one or more of the three ER transmembrane sensors to initiate a complex network of signaling that transiently suppresses protein translation while also enhancing protein folding and proteasomal degradation of misfolded proteins to ensure full recovery from ER stress. Gene disruption studies in mice have provided critical insights into the role of specific signaling components and pathways in the differing responses of animal tissues to ER stress. These studies have emphasized an important contribution of translational repression to sustained insulin synthesis and β-cell viability in experimental models of type-2 diabetes. This has focused attention on the recently discovered small-molecule inhibitors of eIF2α phosphatases that prolong eIF2α phosphorylation to reduce cell death in several animal models of human disease. These compounds show significant cytoprotection in cellular and animal models of neurodegenerative disorders, highlighting a potential strategy for future development of drugs to treat human protein misfolding disorders.