Open Access. Powered by Scholars. Published by Universities.®

Cell Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 6 of 6

Full-Text Articles in Cell Biology

Intraflagellar Transport Protein Ift20 Is Essential For Male Fertility And Spermiogenesis In Mice, Zhengang Zhang, Wei Li, Yong Zhang, Ling Zhang, Maria E. Teves, Hong Liu, Jerome F. Strauss 3rd, Gregory J. Pazour, James A. Foster, Rex A. Hess, Zhibing Zhang Nov 2016

Intraflagellar Transport Protein Ift20 Is Essential For Male Fertility And Spermiogenesis In Mice, Zhengang Zhang, Wei Li, Yong Zhang, Ling Zhang, Maria E. Teves, Hong Liu, Jerome F. Strauss 3rd, Gregory J. Pazour, James A. Foster, Rex A. Hess, Zhibing Zhang

University of Massachusetts Medical School Faculty Publications

Intraflagellar transport (IFT) is a conserved mechanism thought to be essential for the assembly and maintenance of cilia and flagella. However, little is known about its role in mammalian sperm flagella formation. To fill this gap, we disrupted the Ift20 gene in male germ cells. Homozygous mutant mice were infertile with significantly reduced sperm counts and motility. In addition, abnormally shaped elongating spermatid heads and bulbous round spermatids were found in the lumen of the seminiferous tubules. Electron microscopy revealed increased cytoplasmic vesicles, fiber-like structures, abnormal accumulation of mitochondria and a decrease in mature lysosomes. The few developed sperm had ...


Altered Interleukin-10 Signaling In Skeletal Muscle Regulates Obesity-Mediated Inflammation And Insulin Resistance, Sezin Dagdeviren, Dae Young Jung, Eunjung Lee, Randall H. Friedline, Hye Lim Noh, Jong Hun. Kim, Payal R. Patel, Nicholas Tsitsilianos, Andrew V. Tsitsilianos, Duy A. Tran, George H. Tsougranis, Caitlyn C. Kearns, Cecilia P. Uong, Jung Yeon. Kwon, Werner Muller, Ki Won. Lee, Jason K. Kim Nov 2016

Altered Interleukin-10 Signaling In Skeletal Muscle Regulates Obesity-Mediated Inflammation And Insulin Resistance, Sezin Dagdeviren, Dae Young Jung, Eunjung Lee, Randall H. Friedline, Hye Lim Noh, Jong Hun. Kim, Payal R. Patel, Nicholas Tsitsilianos, Andrew V. Tsitsilianos, Duy A. Tran, George H. Tsougranis, Caitlyn C. Kearns, Cecilia P. Uong, Jung Yeon. Kwon, Werner Muller, Ki Won. Lee, Jason K. Kim

University of Massachusetts Medical School Faculty Publications

Skeletal muscle insulin resistance is a major characteristic of obesity and type 2 diabetes. Although obesity-mediated inflammation is causally associated with insulin resistance, the underlying mechanism is unclear. Here, we examined the effects of chronic obesity in mice with muscle-specific overexpression of interleukin-10 (MIL10). After 16 weeks of a high-fat diet (HFD), MIL10 mice became markedly obese but showed improved insulin action compared to that of wild-type mice, which was largely due to increased glucose metabolism and reduced inflammation in skeletal muscle. Since leptin regulates inflammation, the beneficial effects of interleukin-10 (IL-10) were further examined in leptin-deficient ob/ob mice ...


An Alternative Splicing Program Promotes Adipose Tissue Thermogenesis, Santiago Vernia, Yvonne J. K. Edwards, Myoung Souk Han, Julie Cavanagh-Kyros, Tamera Barrett, Jason K. Kim, Roger J. Davis Sep 2016

An Alternative Splicing Program Promotes Adipose Tissue Thermogenesis, Santiago Vernia, Yvonne J. K. Edwards, Myoung Souk Han, Julie Cavanagh-Kyros, Tamera Barrett, Jason K. Kim, Roger J. Davis

University of Massachusetts Medical School Faculty Publications

Alternative pre-mRNA splicing expands the complexity of the transcriptome and controls isoform-specific gene expression. Whether alternative splicing contributes to metabolic regulation is largely unknown. Here we investigated the contribution of alternative splicing to the development of diet-induced obesity. We found that obesity-induced changes in adipocyte gene expression include alternative pre-mRNA splicing. Bioinformatics analysis associated part of this alternative splicing program with sequence specific NOVA splicing factors. This conclusion was confirmed by studies of mice with NOVA deficiency in adipocytes. Phenotypic analysis of the NOVA-deficient mice demonstrated increased adipose tissue thermogenesis and improved glycemia. We show that NOVA proteins mediate a ...


Crispr-Cas9 Nuclear Dynamics And Target Recognition In Living Cells, Hanhui Ma, Li-Chun Tu, Ardalan Naseri, Maximiliaan Huisman, Shaojie Zhang, David Grünwald, Thoru Pederson Aug 2016

Crispr-Cas9 Nuclear Dynamics And Target Recognition In Living Cells, Hanhui Ma, Li-Chun Tu, Ardalan Naseri, Maximiliaan Huisman, Shaojie Zhang, David Grünwald, Thoru Pederson

University of Massachusetts Medical School Faculty Publications

The bacterial CRISPR-Cas9 system has been repurposed for genome engineering, transcription modulation, and chromosome imaging in eukaryotic cells. However, the nuclear dynamics of clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) guide RNAs and target interrogation are not well defined in living cells. Here, we deployed a dual-color CRISPR system to directly measure the stability of both Cas9 and guide RNA. We found that Cas9 is essential for guide RNA stability and that the nuclear Cas9-guide RNA complex levels limit the targeting efficiency. Fluorescence recovery after photobleaching measurements revealed that single mismatches in the guide RNA seed ...


Endothelial Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 Is Critical For Lymphatic Vascular Development And Function, Rachel J. Roth Flach, Chang-An Guo, Laura V. Danai, Joseph C. Yawe, Sharvari Gujja, Yvonne J.K. Edwards, Michael P. Czech May 2016

Endothelial Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 Is Critical For Lymphatic Vascular Development And Function, Rachel J. Roth Flach, Chang-An Guo, Laura V. Danai, Joseph C. Yawe, Sharvari Gujja, Yvonne J.K. Edwards, Michael P. Czech

University of Massachusetts Medical School Faculty Publications

The molecular mechanisms underlying lymphatic vascular development and function are not well understood. Recent studies have suggested a role for endothelial cell (EC) mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) in developmental angiogenesis and atherosclerosis. Here, we show that constitutive loss of EC Map4k4 in mice causes postnatal lethality due to chylothorax, suggesting that Map4k4 is required for normal lymphatic vascular function. Mice constitutively lacking EC Map4k4 displayed dilated lymphatic capillaries, insufficient lymphatic valves, and impaired lymphatic flow; furthermore, primary ECs derived from these animals displayed enhanced proliferation compared with controls. Yeast 2-hybrid analyses identified the Ras GTPase-activating protein ...


Emerging Evidence For Beneficial Macrophage Functions In Atherosclerosis And Obesity-Induced Insulin Resistance, Timothy P. Fitzgibbons, Michael P. Czech Mar 2016

Emerging Evidence For Beneficial Macrophage Functions In Atherosclerosis And Obesity-Induced Insulin Resistance, Timothy P. Fitzgibbons, Michael P. Czech

University of Massachusetts Medical School Faculty Publications

The discovery that obesity promotes macrophage accumulation in visceral fat led to the emergence of a new field of inquiry termed "immunometabolism". This broad field of study was founded on the premise that inflammation and the corresponding increase in macrophage number and activity was a pathologic feature of metabolic diseases. There is abundant data in both animal and human studies that supports this assertation. Established adverse effects of inflammation in visceral fat include decreased glucose and fatty acid uptake, inhibition of insulin signaling, and ectopic triglyceride accumulation. Likewise, in the atherosclerotic plaque, macrophage accumulation and activation results in plaque expansion ...