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University of Massachusetts Medical School

Cellular and Molecular Physiology

Human

Articles 1 - 5 of 5

Full-Text Articles in Life Sciences

A Critical Role Of Vmp1 In Lipoprotein Secretion, Hideaki Morishita, Yan G. Zhao, Norito Tamura, Taki Nishimura, Yuki Kanda, Yuriko Sakamaki, Mitsuyo Okazaki, Dongfang Li, Noboru Mizushima Sep 2019

A Critical Role Of Vmp1 In Lipoprotein Secretion, Hideaki Morishita, Yan G. Zhao, Norito Tamura, Taki Nishimura, Yuki Kanda, Yuriko Sakamaki, Mitsuyo Okazaki, Dongfang Li, Noboru Mizushima

Open Access Articles

Lipoproteins are lipid-protein complexes that are primarily generated and secreted from the intestine, liver, and visceral endoderm and delivered to peripheral tissues. Lipoproteins, which are assembled in the endoplasmic reticulum (ER) membrane, are released into the ER lumen for secretion, but its mechanism remains largely unknown. Here, we show that the release of lipoproteins from the ER membrane requires VMP1, an ER transmembrane protein essential for autophagy and certain types of secretion. Loss of vmp1, but not other autophagy-related genes, in zebrafish causes lipoprotein accumulation in the intestine and liver. Vmp1 deficiency in mice also leads to lipid accumulation in ...


Alpha Cell Function And Gene Expression Are Compromised In Type 1 Diabetes, Marcela Brissova, David Blodgett, Dale L. Greiner, David M. Harlan, Alvin C. Powers Mar 2018

Alpha Cell Function And Gene Expression Are Compromised In Type 1 Diabetes, Marcela Brissova, David Blodgett, Dale L. Greiner, David M. Harlan, Alvin C. Powers

Open Access Articles

Many patients with type 1 diabetes (T1D) have residual beta cells producing small amounts of C-peptide long after disease onset but develop an inadequate glucagon response to hypoglycemia following T1D diagnosis. The features of these residual beta cells and alpha cells in the islet endocrine compartment are largely unknown, due to the difficulty of comprehensive investigation. By studying the T1D pancreas and isolated islets, we show that remnant beta cells appeared to maintain several aspects of regulated insulin secretion. However, the function of T1D alpha cells was markedly reduced, and these cells had alterations in transcription factors constituting alpha and ...


Cellular Differentiation Of Human Monocytes Is Regulated By Time-Dependent Interleukin-4 Signaling And The Transcriptional Regulator Ncor2, Jil Sander, Eicke Latz, Andreas Schlitzer Dec 2017

Cellular Differentiation Of Human Monocytes Is Regulated By Time-Dependent Interleukin-4 Signaling And The Transcriptional Regulator Ncor2, Jil Sander, Eicke Latz, Andreas Schlitzer

Open Access Articles

Human in vitro generated monocyte-derived dendritic cells (moDCs) and macrophages are used clinically, e.g., to induce immunity against cancer. However, their physiological counterparts, ontogeny, transcriptional regulation, and heterogeneity remains largely unknown, hampering their clinical use. High-dimensional techniques were used to elucidate transcriptional, phenotypic, and functional differences between human in vivo and in vitro generated mononuclear phagocytes to facilitate their full potential in the clinic. We demonstrate that monocytes differentiated by macrophage colony-stimulating factor (M-CSF) or granulocyte macrophage colony-stimulating factor (GM-CSF) resembled in vivo inflammatory macrophages, while moDCs resembled in vivo inflammatory DCs. Moreover, differentiated monocytes presented with profound transcriptomic ...


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 ...


Human Basal Body Basics, Anastassiia Vertii, Hui-Fang Hung, Heidi Hehnly, Stephen J. Doxsey Mar 2016

Human Basal Body Basics, Anastassiia Vertii, Hui-Fang Hung, Heidi Hehnly, Stephen J. Doxsey

Open Access Articles

In human cells, the basal body (BB) core comprises a ninefold microtubule-triplet cylindrical structure. Distal and subdistal appendages are located at the distal end of BB, where they play indispensable roles in cilium formation and function. Most cells that arrest in the G0 stage of the cell cycle initiate BB docking at the plasma membrane followed by BB-mediated growth of a solitary primary cilium, a structure required for sensing the extracellular environment and cell signaling. In addition to the primary cilium, motile cilia are present in specialized cells, such as sperm and airway epithelium. Mutations that affect BB function result ...