Splice variants of Enigma homolog, differentially expressed during heart development, promote or prevent hypertrophy

Aims Proteins with a PDZ (for PSD-95, DLG, ZO-1) and one to three LIM (for Lin11, Isl-1, Mec-3) domains are scaffolding sarcomeric and cytoskeletal elements that form structured muscle fibres and provide for the link to intracellular signalling by selectively associating protein kinases, ion channels, and transcription factors with the mechanical stress-strain sensors. Enigma homolog (ENH) is a PDZ-LIM protein with four splice variants: ENH1 with an N-terminal PDZ domain and three C-terminal LIM domains and ENH2, ENH3, and ENH4 without LIM domains. We addressed the functional role of ENH alternative splicing. Methods and results We studied the expression of the four ENH isoforms in the heart during development and in a mouse model of heart hypertrophy. All four isoforms are expressed in the heart but the pattern of expression is clearly different between embryonic, neonatal, and adult stages. ENH1 appears as the embryonic isoform, whereas ENH2, ENH3, and ENH4 are predominant in adult heart. Moreover, alternative splicing of ENH was changed following induction of heart hypertrophy, producing an ENH isoform pattern similar to that of neonatal heart. Next, we tested a possible causal role of ENH1 and ENH4 in the development of cardiac hypertrophy. When overexpressed in rat neonatal cardiomyocytes, ENH1 promoted the expression of hypertrophy markers and increased cell volume, whereas, on the contrary, ENH4 overexpression prevented these changes. Conclusion Antagonistic splice variants of ENH may play a central role in the adaptive changes of the link between mechanical stress-sensing and signalling occurring during embryonic development and/or heart hypertroph

pre-Sペプチドを含むB型肝炎ウイルス外被タンパク質に関する研究

本文データは平成22年度国立国会図書館の学位論文(博士)のデジタル化実施により作成された画像ファイルを基にpdf変換したものである京都大学0048新制・論文博士博士(農学)乙第8019号論農博第1796号新制||農||640(附属図書館)学位論文||H4||N2518(農学部図書室)UT51-92-U255(主査)教授 左右田 健次, 教授 駒野 徹, 教授 清水 昌学位規則第4条第2項該当Doctor of Agricultural ScienceKyoto UniversityDFA

Ultrahigh-sensitive wireless QCM with bio-nanocapsules

Quartz-crystal-microbalance (QCM)biosensor is a mass-sensitive biosensor, and its sensitivity in detecting target proteins can be improved with weighted detection antibodies. In this communication, we propose a mass-amplified detection of biomarkers by bio-nanocapsules (BNCs)in wireless high-frequency multichannel QCM biosensor. BNC exhibits molecular mass of 6.57 MDa and possesses many immunoglobulin-G (IgG)Fc-binding Z domains on its surface, making it possible to display ∼60 antibodies in an oriented immobilization manner. We find that by reinforcing the bond strength between the Z domain and the Fc part of antibody with the cross-linker, a high sensitive detection of biomarkers with QCM is realized. We used multichanel wireless QCM system with fundamental resonance frequencies above 54 MHz and performed detection of C-reactive protein. The detection limit is lower than 10 pg/mL, confirming that combination of BNC and wireless high-frequency QCM allows high sensitivity detection of biomarkers

Mechanism of affinity-enhanced protein adsorption on bio-nanocapsules studied by viscoelasticity measurement with wireless QCM biosensor

Recent advances in functionalized bio-nanocapsules (BNCs) have allowed a significant sensitivity enhancement in label-free biosensors. It is suggested that sensitivity amplification is caused by the higher binding affinity of BNCs to target antibodies. We here study the high-affinity interaction mechanism between BNCs and antibodies with wireless high-frequency QCM biosensors. We first confirmed the higher affinity between BNCs and human immunoglobulin G. We then found that the number of binding sites for the target antibody significantly increases by immobilizing BNC molecules on the sensor surface. We finally studied changes in viscoelasticity near the sensor surface using a MEMS wireless QCM biosensor using up to the ninth overtone (522 MHz). The inversely determined effective shear modulus on BNCs was found to be significantly lower than that on a standard surface on which the receptor molecules were immobilized. We have thus clarified that this surface flexibility achieves high affinity with target antibodies.This is the Accepted Manuscript version of an article accepted for publication in Japanese Journal of Applied Physics. IOP Publishing Ltd are not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at https://doi.org/10.35848/1347-4065/ab78e1

Functions of Fasciculation and Elongation Protein Zeta-1 (FEZ1) in the Brain

Fasciculation and elongation protein zeta-1 (FEZ1) is a mammalian ortholog of the Caenorhabditis elegans UNC-76 protein that possesses four coiled-coil domains and a nuclear localization signal. It is mainly expressed in the brain. Suppression of FEZ1 expression in cultured embryonic neurons causes deficiency of neuronal differentiation. Recently, proteomic techniques revealed that FEZ1 interacts with various intracellular partners, such as signaling, motor, and structural proteins. FEZ1 was shown to act as an antiviral factor. The findings reported so far indicate that FEZ1 is associated with neuronal development, neuropathologies, and viral infection. Based on these accumulating evidences, we herein review the biological functions of FEZ1