scholarly journals splitGFP Technology Reveals Dose-Dependent ER-Mitochondria Interface Modulation by α-Synuclein A53T and A30P Mutants

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1072 ◽  
Author(s):  
Tito Calì ◽  
Denis Ottolini ◽  
Mattia Vicario ◽  
Cristina Catoni ◽  
Francesca Vallese ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Mitochondrial Function ◽  
Cell Metabolism ◽  
Loss Of Function ◽  
Function Mechanism ◽  
Dose Dependent ◽  
Familial Parkinson’S Disease ◽  
Interface Modulation

Familial Parkinson’s disease (PD) is associated with duplication or mutations of α-synuclein gene, whose product is a presynaptic cytosolic protein also found in mitochondria and in mitochondrial-associated ER membranes. We have originally shown the role of α-syn as a modulator of the ER-mitochondria interface and mitochondrial Ca2+ transients, suggesting that, at mild levels of expression, α-syn sustains cell metabolism. Here, we investigated the possibility that α-syn action on ER-mitochondria tethering could be compromised by the presence of PD-related mutations. The clarification of this aspect could contribute to elucidate key mechanisms underlying PD. The findings reported so far are not consistent, possibly because of the different methods used to evaluate ER-mitochondria connectivity. Here, the effects of the PD-related α-syn mutations A53T and A30P on ER-mitochondria relationship were investigated in respect to Ca2+ handling and mitochondrial function using a newly generated SPLICS sensor and aequorin-based Ca2+measurements. We provided evidence that A53T and A30P amino acid substitution does not affect the ability of α-syn to enhance ER/mitochondria tethering and mitochondrial Ca2+ transients, but that this action was lost as soon as a high amount of TAT-delivered A53T and A30P α-syn mutants caused the redistribution of α-syn from cytoplasm to foci. Our results suggest a loss of function mechanism and highlight a possible connection between α-syn and ER-mitochondria Ca2+ cross-talk impairment to the pathogenesis of PD.

scholarly journals A Novel Pinkish-White Flower Color Variant Is Caused by a New Allele of Flower Color Gene W1 in Wild Soybean (Glycine soja)

Agronomy ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1001
Author(s):  
Jagadeesh Sundaramoorthy ◽  
Gyu Tae Park ◽  
Hyun Jo ◽  
Jeong-Dong Lee ◽  
Hak Soo Seo ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Functional Activity ◽  
Glycine Soja ◽  
Wild Soybean ◽  
Flower Color ◽  
Loss Of Function ◽  
Protein Variation ◽  
Color Variant ◽  
Color Gene

The enzyme flavonoid 3′,5′-hydroxylase (F3′5′H) plays an important role in producing anthocyanin pigments in soybean. Loss of function of the W1 locus encoding F3′5′H always produces white flowers. However, few color variations have been reported in wild soybean. In the present study, we isolated a new color variant of wild soybean accession (IT261811) with pinkish-white flowers. We found that the flower’s pinkish-white color is caused by w1-s3, a single recessive allele of W1. The SNP detected in the mutant caused amino acid substitution (A304S) in a highly conserved SRS4 domain of F3′5′H proteins. On the basis of the results of the protein variation effect analyzer (PROVEAN) tool, we suggest that this mutation may lead to hypofunctional F3′5′H activity rather than non-functional activity, which thereby results in its pinkish-white color.

scholarly journals Amino acid substitution reveals the role of V-shape helix on construction of yeast carboxypeptidase Y

2014 ◽  
Vol 14 (1) ◽  
pp. 27-41 ◽  
Author(s):  
Mai Makino ◽  
Takehiko Sahara ◽  
Naoki Morita ◽  
Hiroshi Ueno
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Carboxypeptidase Y

Stabilization of the angiotensin-(1–7) receptor Mas through interaction with PSD95

2013 ◽  
Vol 453 (3) ◽  
pp. 345-356 ◽  
Author(s):  
Weihua Bian ◽  
Licui Sun ◽  
Longyan Yang ◽  
Ji-Feng Li ◽  
Jia Hu ◽  
...  
Keyword(s):  
Proteasome Inhibitor Mg132 ◽  
Loss Of Function ◽  
Mas Receptor ◽  
C Terminus ◽  
Proteolytic Pathway ◽  
Intracellular Regulation ◽  
Subsequent Degradation ◽  
Ubiquitin Proteasome ◽  
Dose Dependent

The functions and signalling mechanisms of the Ang-(1–7) [angiotensin-(1–7)] receptor Mas have been studied extensively. However, less attention has been paid to the intracellular regulation of Mas protein. In the present study, PSD95 (postsynaptic density 95), a novel binding protein of Mas receptor, was identified, and their association was characterized further. Mas specifically interacts with PDZ1-2, but not the PDZ3, domain of PSD95 via Mas-CT (Mas C-terminus), and the last four amino acids [ETVV (Glu-Thr-Val-Val)] of Mas-CT were determined to be essential for this interaction, as shown by GST pull-down, co-immunoprecipitation and confocal co-localization experiments. Gain-of-function and loss-of-function studies indicated that PSD95 enhanced Mas protein expression by increasing the stabilization of the receptor. Mas degradation was robustly inhibited by the proteasome inhibitor MG132 in time- and dose-dependent manners, and the expression of PSD95 impaired Mas ubiquitination, indicating that the PSD95–Mas association inhibits Mas receptor degradation via the ubiquitin–proteasome proteolytic pathway. These findings reveal a novel mechanism of Mas receptor regulation by which its expression is modulated at the post-translational level by ubiquitination, and clarify the role of PSD95, which binds directly to Mas, blocking the ubiquitination and subsequent degradation of the receptor via the ubiquitin–proteasome proteolytic pathway.

scholarly journals An Isolated Hypogonadotropic Hypogonadism due to a L102P Inactivating Mutation of KISS1R/GPR54 in a Large Family

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Ahmad J. Alzahrani ◽  
Azzam Ahmad ◽  
Tariq Alhazmi ◽  
Lujin Ahmad
Keyword(s):  
Amino Acid ◽  
Extended Family ◽  
Hypogonadotropic Hypogonadism ◽  
Large Family ◽  
Homozygous Mutation ◽  
Loss Of Function ◽  
Gonadotropin Secretion ◽  
Healthy Baby ◽  
Inactivating Mutation

KISS1R (GPR54) mutations have been reported in several patients with congenital normosmic idiopathic hypogonadotropic hypogonadism (nIHH). We aim to describe in detail nIHH patients with KISS1R (GPR54) mutations belonging to one related extended family and to review the literature. A homozygous mutation (T305C) leading to a leucine substitution with proline (L102P) was found in three affected kindred (2 males and 1 female) from a consanguineous Saudi Arabian family. This residue is localized within the first exoloop of the receptor, affects a highly conserved amino acid, perturbs the conformation of the transmembrane segment, and impairs its function. In the affected female, a combined gonadotropin administration restored regular period and ovulation and she conceived with a healthy baby boy after 4 years of marriage. We showed that a loss-of-function mutation (p.Tyr305C) in the KISS1R gene can cause (L102P) KISS1 receptor dysfunction and familial nIHH, revealing the crucial role of this amino acid in KISS1R function. The observed restoration of periods and later on pregnancy by an exogenous gonadotropin administration further support, in humans, that the KISS1R mutation has no other harmful effects on the patients apart from the gonadotropin secretion impairment.

scholarly journals Cancer cell metabolism: the essential role of the nonessential amino acid, glutamine

2017 ◽  
Vol 36 (10) ◽  
pp. 1302-1315 ◽  
Author(s):  
Ji Zhang ◽  
Natalya N Pavlova ◽  
Craig B Thompson
Keyword(s):  
Amino Acid ◽  
Cancer Cell ◽  
Essential Role ◽  
Cell Metabolism ◽  
Nonessential Amino Acid ◽  
Cancer Cell Metabolism
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