bims-bicyki 2020-11-08 papers

Issue of 2020‒11‒08
five papers selected by
Céline Gagnieux
École Polytechnique Fédérale de Lausanne (EPFL)

CEN Case Rep. 2020 Nov 03.

Renal epithelial and stromal tumor with a multiple cystic lesion localized in the upper portion of the right kidney.

Masato Sawamura, Naoki Sawa, Masayuki Yamanouchi, Daisuke Ikuma, Akinari Sekine, Hiroki Mizuno, Tatsuya Suwabe, Junichi Hoshino, Kei Kono, Keiichi Kinowaki, Kenichi Ohashi, Yoji Nagashima, Yoshifumi Ubara.

A 60-year-old Japanese woman was admitted because of the polycystic mass with right flank pain localized in the upper portion of the right kidney. Right nephrectomy was performed because the mass lesion had continuously increased in size over the past 10 years. A surgical specimen showed histology consistent with a mixed epithelial and stromal tumor, which is closely related to multilocular cystic nephroma, and was diagnosed by a defined capsule between the cystic mass lesion and normal renal tissue by CT and MRI, and histology. Localized renal cystic disease that does not have a capsule was excluded from differential diagnosis.

Keywords: Autosomal dominant polycystic kidney disease; Multilocular cystic nephroma; Renal epithelial and stromal tumor; Unilateral renal cystic disease

DOI: https://doi.org/10.1007/s13730-020-00548-9

Curr Med Chem. 2020 Nov 01.

Intracellular calcium homeostasis and kidney disease.

Na Song, Ming Yang, Hao Zhang, Shi-Kun Yang.

Kidney disease is a serious health problem that burdens our healthcare system. It is crucial to find the accurate pathogenesis of various types of kidney disease to provide guidance for precise therapies for patients suffered from these diseases. However,the exact molecular mechanisms underlying these diseases have not been fully understood. Disturbance of calcium homeostasis in renal cells plays a fundamental role in the development of various types of kidney disease,such as primary glomerular disease, diabetic nephropathy, acute kidney injury and polycystic kidney disease,through promoting cell proliferation,stimulating extracellular matrix accumulation, aggravating podocyte injury, disrupting cellular energetics as well as disregulating cell survival and death dynamics.As a result, preventing the disturbance of calcium homeostasis in specific renal cells(such as tubular cells, podocytes and mesangial cells) is becoming one of the most promosing therapeutic stratergies in the treatment of kidney disease.The endoplasmic reticulum and mitochondria are two vital organelles in this process. Calcium ions cycle between the endoplasmic reticulum and mitochondria at the conjugation of these two organelles known as the mitochondria-associated endoplasmic reticulum membrane, maintaining calcium homeostasis. The pharmacologic modulation of cellular calcium homeostasis can be viewed as a novel therapeutic method to renal diseases. Here, we will introduce the calcium homeostasis under physiological conditions and the disturbance of calcium homeostasis in kidney diseases. We will focus on the calcium homeostasis regulation in renal cells (including tubular cells, podocytes and mesangial cells), especially that in the mitochondria-associated endoplasmic reticulum membranes of these renal cells.

Keywords: Calcium homeostasis; cellular; endoplasmic reticulum; kidney; mitochondria; mitochondria-associated endoplasmic reticulum membrane.

DOI: https://doi.org/10.2174/0929867327666201102114257

Biomolecules. 2020 Nov 01. pii: E1504. [Epub ahead of print]10(11):

Potential Roles of O-GlcNAcylation in Primary Cilia- Mediated Energy Metabolism.

Jie L Tian, Farzad Islami Gomeshtapeh.

The primary cilium, an antenna-like structure on most eukaryotic cells, functions in transducing extracellular signals into intracellular responses via the receptors and ion channels distributed along it membrane. Dysfunction of this organelle causes an array of human diseases, known as ciliopathies, that often feature obesity and diabetes; this indicates the primary cilia's active role in energy metabolism, which it controls mainly through hypothalamic neurons, preadipocytes, and pancreatic β-cells. The nutrient sensor, O-GlcNAc, is widely involved in the regulation of energy homeostasis. Not only does O-GlcNAc regulate ciliary length, but it also modifies many components of cilia-mediated metabolic signaling pathways. Therefore, it is likely that O-GlcNAcylation (OGN) plays an important role in regulating energy homeostasis in primary cilia. Abnormal OGN, as seen in cases of obesity and diabetes, may play an important role in primary cilia dysfunction mediated by these pathologies.

Keywords: O-GlcNAc; diabetes; energy homeostasis; obesity; primary cilia

DOI: https://doi.org/10.3390/biom10111504

Biophys J. 2020 Oct 30. pii: S0006-3495(20)30851-1. [Epub ahead of print]

C-terminal tail polyglycylation and polyglutamylation alter microtubule mechanical properties.

Kathryn P Wall, Harold Hart, Thomas Lee, Cynthia Page, Taviare L Hawkins, Loren Hough.

Microtubules are biopolymers that perform diverse cellular functions. Microtubule behavior regulation occurs in part through post-translational modification of both the α- and β- subunits of tubulin. One class of modifications is the heterogeneous addition of glycine and/or glutamate residues to the disordered C-terminal tails (CTTs) of tubulin. Due to their prevalence in stable, high stress cellular structures such as cilia, we sought to determine if these modifications alter microtubules' intrinsic stiffness. Here we describe the purification and characterization of differentially-modified pools of tubulin from Tetrahymena thermophila. We found that post-translational modifications do affect microtubule stiffness, but do not affect the number of protofilaments incorporated into microtubules. We measured the spin dynamics of nuclei in the CTT backbone by nuclear magnetic resonance spectroscopy to explore the mechanism of this change. Our results show that the α-tubulin CTT does not protrude out from the microtubule surface, as is commonly depicted in models, but instead interacts with the dimer's surface. Thus suggests that the interactions of the α-tubulin CTT with the tubulin body contributes to the stiffness of the assembled microtubule, thus providing insight into the mechanism by which polyglycylation and polyglutamylation can alter microtubule mechanical properties.

DOI: https://doi.org/10.1016/j.bpj.2020.09.040

Curr Opin Struct Biol. 2020 Oct 29. pii: S0959-440X(20)30173-1. [Epub ahead of print]66 32-40

Charting the complex composite nature of centrosomes, primary cilia and centriolar satellites.

Raksha Devi, Laurence Pelletier, Suzanna L Prosser.

The centrosome and its associated structures of the primary cilium and centriolar satellites have been established as central players in a plethora of cellular processes ranging from cell division to cellular signaling. Consequently, defects in the structure or function of these organelles are linked to a diverse range of human diseases, including cancer, microcephaly, ciliopathies, and neurodegeneration. To understand the molecular mechanisms underpinning these diseases, the biology of centrosomes, cilia, and centriolar satellites has to be elucidated. Central to solving this conundrum is the identification, localization, and functional analysis of all the proteins that reside and interact with these organelles. In this review, we discuss the technological breakthroughs that are dissecting the molecular players of these enigmatic organelles with unprecedented spatial and temporal resolution.

DOI: https://doi.org/10.1016/j.sbi.2020.10.006