Adam C. Labonte, Annie-Carole Tosello-Trampont, and Young S. HahnMol. Cells 2014; 37(4): 275-285 https://doi.org/10.14348/molcells.2014.2374
Abstract : Macrophages, found in circulating blood as well as integrated into several tissues and organs throughout the body, represent an important first line of defense against disease and a necessary component of healthy tissue homeostasis. Additionally, macrophages that arise from the differentiation of monocytes recruited from the blood to inflamed tissues play a central role in regulating local inflammation. Studies of macrophage activation in the last decade or so have revealed that these cells adopt a staggering range of phenotypes that are finely tuned responses to a variety of different stimuli, and that the resulting subsets of activated macrophages play critical roles in both progression and resolution of disease. This review summarizes the current understanding of the contributions of differentially polarized macrophages to various infectious and inflammatory diseases and the ongoing effort to develop novel therapies that target this key aspect of macrophage biology.
Kyung S. Lee, Jung-Eun Park, Young Hwi Kang, Tae-Sung Kim, and Jeong K. BangMol. Cells 2014; 37(4): 286-294 https://doi.org/10.14348/molcells.2014.0002
Abstract : Mammalian polo-like kinase 1 (Plk1) has been studied intensively as a key regulator of various cell cycle events that are critical for proper M-phase progression. The polo-box domain (PBD) present in Plk1’s C-terminal non-catalytic region has been shown to play a central role in targeting the N-terminal kinase domain of Plk1 to specific subcellular locations. Subsequent studies reveal that PBD binds to a phosphorylated motif generated by one of the two mechanisms - self-priming by Plk1 itself or non-self-priming by a Pro-directed kinase, such as Cdc2. Here, we comparatively review the differences in the biochemical steps of these mechanisms and discuss their physiological significance. Considering the diverse functions of Plk1 during the cell cycle, a better understanding of how the catalytic activity of Plk1 functions in concert with its cis-acting PBD and how this coordinated process is intricately regulated to promote Plk1 functions will be important for providing new insights into different mechanisms underlying various Plk1-mediated biological events that occur at the multiple stages of the cell cycle.
Sangjin Park, Jun Young Sonn, Yangkyun Oh, Chunghun Lim, and Joonho ChoeMol. Cells 2014; 37(4): 295-301 https://doi.org/10.14348/molcells.2014.2371
Abstract : SIFamide receptor (SIFR) is a
Xian-Ju Huang, Hong-Xiao Zhang, Huili Wang, Kai Xiong, Ling Qin, and Honglin LiuMol. Cells 2014; 37(4): 302-306 https://doi.org/10.14348/molcells.2014.2209
Abstract : Myostatin represses muscle growth by negatively regulating the number and size of muscle fibers. Myostatin loss-of-function can result in the double-muscling phenotype and increased muscle mass. Thus, knockout of myostatin gene could improve the quality of meat from mammals. In the present study, zinc finger nucleases, a useful tool for generating gene knockout animals, were designed to target exon 1 of the myostatin gene. The designed ZFNs were introduced into porcine primary fibroblasts and early implantation embryos
Mi-Rae Lee, Hyeseon Kim, and Taeck J. JeonMol. Cells 2014; 37(4): 307-313 https://doi.org/10.14348/molcells.2014.2309
Abstract : Cell migration requires a defined cell polarity which is formed by diverse cytoskeletal components differentially localized to the poles of cells to extracellular signals. Rap-GAP3 transiently and rapidly translocates to the cell cortex in response to chemoattractant stimulation and localizes to the leading edge of migrating cells. Here, we examined localization of truncated RapGAP3 proteins and found that the I/LWEQ domain in the central region of RapGAP3 was sufficient for posterior localization in migrating cells, as opposed to leading-edge localization of full-length Rap-GAP3. All truncated proteins accumulated at the leading edge of migrating cells exhibited clear translocation to the cell cortex in response to stimulation, whereas proteins localized to the posterior in migrating cells displayed no translocation to the cortex. The I/LWEQ domain appears to passively accumulate at the posterior region in migrating cells due to exclusion from the extended front region in response to chemoattractant stimulation rather than actively being localized to the back of cells. Our results suggest that posterior localization of the I/LWEQ domain of RapGAP3 is likely related to F-actin, which has probably different properties compared to newly formed F-actin at the leading edge of migrating cells, at the lateral and posterior regions of the cell.
Sena Yoon, Eunji Han, Young-Chul Choi, Honghwan Kee, Yongsu Jeong, Jaeseung Yoon, and Kwanghee BaekMol. Cells 2014; 37(4): 314-321 https://doi.org/10.14348/molcells.2014.2360
Abstract : CDK2 is a key regulator of cell cycle progression. In this study, we screened for miRNAs targeting CDK2 using a luciferase-3′-untranslated region reporter assay. Among 11 hit miRNAs, miR-509-3p reduced CDK2 protein levels and significantly inhibited cancer cell growth. Microarray, Western blotting, and luciferase reporter analyses revealed additional targets of miR-509-3p, including Rac1 and PIK3C2A. Overexpression of miR-509-3p induced G1 cell-cycle arrest and inhibited colony formation and migration. RNAi experiments indicated that the growth-inhibitory effects of miR-509-3p may occur through down-regulation of CDK2, Rac1, and PIK3C2A. Targeting of multiple growth regulatory genes by miR-509-3p may contribute to effective anti-cancer therapy.
HyunSook Lee, Samikshan Dutta, and Il Soo MoonMol. Cells 2014; 37(4): 322-329 https://doi.org/10.14348/molcells.2014.2377
Sun-Hye Shin, Sangkyu Lee, Jong-Sup Bae, Jun-Goo Jee, Hee-Jae Cha, and You Mie LeeMol. Cells 2014; 37(4): 330-336 https://doi.org/10.14348/molcells.2014.0003
Abstract : Thymosin beta4 (TB4) has multiple functions in cellular response in processes as diverse as embryonic organ development and the pathogeneses of disease, especially those associated with cardiac coronary vessels. However, the specific roles played by TB4 during heart valve development in vertebrates are largely unknown. Here, we identified a novel function of TB4 in endothelialmesenchymal transformation (EMT) in cardiac valve endocardial cushions in zebrafish. The expressions of thymosin family members in developing zebrafish embryos were determined by whole mount
Mi Kyung Choi, Ikjoo Seong, Seon Ah Kang, and Jaesang KimMol. Cells 2014; 37(4): 337-344 https://doi.org/10.14348/molcells.2014.0021
Abstract : Adipose-derived stem cells represent a type of mesenchymal stem cells with the attendant capacity to self-renew and differentiate into multiple cell lineages. We have performed a microarray-based gene expression profiling of osteogenic differentiation and found that the transcription factor Sox11 is down-regulated during the process. Functional assays demonstrate that down-regulation of Sox11 is required for an efficient differentiation. Furthermore, results from forced expression of constitutively-active and dominant-negative derivatives of Sox11 indicate that Sox11 functions as a transcriptional activator in inhibiting osteogenesis. Sox11 thus represents a novel regulator of osteogenesis whose expression and activity can be potentially manipulated for controlled differentiation.
Hey-Kyeong Jeong, Kyung-Min Ji, Kyoung-Jin Min, Insup Choi, Dong-Joo Choi, Ilo Jou, and Eun-Hye JoeMol. Cells 2014; 37(4): 345-355 https://doi.org/10.14348/molcells.2014.0046
Abstract : Mitigating secondary delayed neuronal injury has been a therapeutic strategy for minimizing neurological symptoms after several types of brain injury. Interestingly, secondary neuronal loss appeared to be closely related to functional loss and/or death of astrocytes. In the brain damage induced by agonists of two glutamate receptors, N-ethyl-D-aspartic acid (NMDA) and kainic acid (KA), NMDA induced neuronal death within 3 h, but did not increase further thereafter. However, in the KA-injected brain, neuronal death was not obviously detectable even at injection sites at 3 h, but extensively increased to encompass the entire hemisphere at 7 days. Brain inflammation, a possible cause of secondary neuronal damage, showed little differences between the two models. Importantly, however, astrocyte behavior was completely different. In the NMDA-injected cortex, the loss of glial fibrillary acidic protein-expressing (GFAP+) astrocytes was confined to the injection site until 7 days after the injection, and astrocytes around the damage sites showed extensive gliosis and appeared to isolate the damage sites. In contrast, in the KA-injected brain, GFAP+ astrocytes, like neurons, slowly, but progressively, disappeared across the entire hemisphere. Other markers of astrocytes, including S100β, glutamate transporter EAAT2, the potassium channel Kir4.1 and glutamine synthase, showed patterns similar to that of GFAP in both NMDA- and KA-injected cortexes. More importantly, astrocyte disappearance and/or functional loss preceded neuronal death in the KA-injected brain. Taken together, these results suggest that loss of astrocyte support to neurons may be a critical cause of delayed neuronal death in the injured brain.