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Wei-Chien Hung Shih-Hsun Chen Colin D. Paul Kimberly M. Stroka Ying-Chun Lo Joy T. Yang Konstantinos Konstantopoulos 《The Journal of cell biology》2013,202(5):807-824
Using a microchannel assay, we demonstrate that cells adopt distinct signaling strategies to modulate cell migration in different physical microenvironments. We studied α4β1 integrin–mediated signaling, which regulates cell migration pertinent to embryonic development, leukocyte trafficking, and melanoma invasion. We show that α4β1 integrin promotes cell migration through both unconfined and confined spaces. However, unlike unconfined (2D) migration, which depends on enhanced Rac1 activity achieved by preventing α4/paxillin binding, confined migration requires myosin II–driven contractility, which is increased when Rac1 is inhibited by α4/paxillin binding. This Rac1–myosin II cross talk mechanism also controls migration of fibroblast-like cells lacking α4β1 integrin, in which Rac1 and myosin II modulate unconfined and confined migration, respectively. We further demonstrate the distinct roles of myosin II isoforms, MIIA and MIIB, which are primarily required for confined and unconfined migration, respectively. This work provides a paradigm for the plasticity of cells migrating through different physical microenvironments. 相似文献
73.
Mark P. Zanin Kimberly D. Mackenzie Heshan Peiris Melanie A. Pritchard Damien J. Keating 《Journal of neurochemistry》2013,124(3):290-299
We have previously shown that Regulator of Calcineurin 1 (RCAN1) regulates multiple stages of vesicle exocytosis. However, the mechanisms by which RCAN1 affects secretory vesicle exocytosis and quantal release kinetics remain unknown. Here, we use carbon fibre amperometry to detect exocytosis from chromaffin cells and identify these underlying mechanisms. We observe reduced exocytosis with repeated stimulations in chromaffin cells over‐expressing RCAN1 (RCAN1ox), but not in wild‐type (WT) cells, indicating a negative effect of RCAN1 on vesicle recycling and endocytosis. Acute exposure to calcineurin inhibitors, cyclosporine A and FK‐506, replicates this effect in WT cells but has no additional effect in RCAN1ox cells. When we chronically expose WT cells to cyclosporine A and FK‐506 we find that catecholamine release per vesicle and pre‐spike foot (PSF) signal parameters are decreased, similar to that in RCAN1ox cells. Inhibiting calcineurin activity in RCAN1ox cells has no additional effect on the amount of catecholamine release per vesicle but further reduces PSF signal parameters. Although electron microscopy studies indicate these changes are not because of altered vesicle number or distribution in RCAN1ox cells, the smaller vesicle and dense core size we observe in RCAN1ox cells may underlie the reduced quantal release in these cells. Thus, our results indicate that RCAN1 most likely affects vesicle recycling and quantal release kinetics via the inhibition of calcineurin activity. 相似文献
74.
Kimberly P. McCallum Freya O. McDougall Roger S. Seymour 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2013,183(7):867-876
Pollination biology is often associated with mutualistic interactions between plants and their animal pollen vectors, with energy rewards as the foundation for co-evolution. Energy is supplied as food (often nectar from flowers) or as heat (in sun-tracking or thermogenic plants). The requirements of pollinators for these resources depend on many factors, including the costs of living, locomotion, thermoregulation and behaviour, all of which are influenced by body size. These requirements are modified by the availability of energy offered by plants and environmental conditions. Endothermic insects, birds and bats are very effective, because they move faster and are more independent of environmental temperatures, than are ectothermic insects, but they are energetically costly for the plant. The body size of endothermic pollinators appears to be influenced by opposing requirements of the animals and plants. Large body size is advantageous for endotherms to retain heat. However, plants select for small body size of endotherms, as energy costs of larger size are not matched by increases in flight speed. If high energy costs of endothermy cannot be met, birds and mammals employ daily torpor, and large insects reduce the frequency of facultative endothermy. Energy uptake can be limited by the time required to absorb the energy or eliminate the excess water that comes with it. It can also be influenced by variations in climate that determine temperature and flowering season. 相似文献
75.
John N. Freskos Bethel Asmelash Kimberly R. Gaston Amol Karwa Tim A. Marzan Maureen A. Nickols Thomas E. Rogers Tasha Schoenstein Carolyn J. Sympson Bich Vu 《Bioorganic & medicinal chemistry letters》2013,23(20):5566-5570
We describe the synthesis, MMP-2 and 9 potency, and in vitro evaluation of a series of α-sulfone hydroxmate MMP inhibitors conjugated to a series of dyes with different absorption/emission lamina maxima’s that can be used to visualize tumors. 相似文献
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Les N. Harris Kimberly L. Howland Matthew W. Kowalchuk Robert Bajno Melissa M. Lindsay Eric B. Taylor 《Ecology and evolution》2013,3(1):145-161
Resolving the genetic population structure of species inhabiting pristine, high latitude ecosystems can provide novel insights into the post‐glacial, evolutionary processes shaping the distribution of contemporary genetic variation. In this study, we assayed genetic variation in lake trout (Salvelinus namaycush) from Great Bear Lake (GBL), NT and one population outside of this lake (Sandy Lake, NT) at 11 microsatellite loci and the mtDNA control region (d‐loop). Overall, population subdivision was low, but significant (global FST θ = 0.025), and pairwise comparisons indicated that significance was heavily influenced by comparisons between GBL localities and Sandy Lake. Our data indicate that there is no obvious genetic structure among the various basins within GBL (global FST = 0.002) despite the large geographic distances between sampling areas. We found evidence of low levels of contemporary gene flow among arms within GBL, but not between Sandy Lake and GBL. Coalescent analyses suggested that some historical gene flow occurred among arms within GBL and between GBL and Sandy Lake. It appears, therefore, that contemporary (ongoing dispersal and gene flow) and historical (historical gene flow and large founding and present‐day effective population sizes) factors contribute to the lack of neutral genetic structure in GBL. Overall, our results illustrate the importance of history (e.g., post‐glacial colonization) and contemporary dispersal ecology in shaping genetic population structure of Arctic faunas and provide a better understanding of the evolutionary ecology of long‐lived salmonids in pristine, interconnected habitats. 相似文献
78.
Mark P. Peterson Kimberly A. Rosvall Jeong-Hyeon Choi Charles Ziegenfus Haixu Tang John K. Colbourne Ellen D. Ketterson 《PloS one》2013,8(4)
Despite sharing much of their genomes, males and females are often highly dimorphic, reflecting at least in part the resolution of sexual conflict in response to sexually antagonistic selection. Sexual dimorphism arises owing to sex differences in gene expression, and steroid hormones are often invoked as a proximate cause of sexual dimorphism. Experimental elevation of androgens can modify behavior, physiology, and gene expression, but knowledge of the role of hormones remains incomplete, including how the sexes differ in gene expression in response to hormones. We addressed these questions in a bird species with a long history of behavioral endocrinological and ecological study, the dark-eyed junco (Junco hyemalis), using a custom microarray. Focusing on two brain regions involved in sexually dimorphic behavior and regulation of hormone secretion, we identified 651 genes that differed in expression by sex in medial amygdala and 611 in hypothalamus. Additionally, we treated individuals of each sex with testosterone implants and identified many genes that may be related to previously identified phenotypic effects of testosterone treatment. Some of these genes relate to previously identified effects of testosterone-treatment and suggest that the multiple effects of testosterone may be mediated by modifying the expression of a small number of genes. Notably, testosterone-treatment tended to alter expression of different genes in each sex: only 4 of the 527 genes identified as significant in one sex or the other were significantly differentially expressed in both sexes. Hormonally regulated gene expression is a key mechanism underlying sexual dimorphism, and our study identifies specific genes that may mediate some of these processes. 相似文献
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