Role of Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase 1 in Nodule Development of Soybean

2021 ◽  
pp. 153543
Author(s):  
Ali Izadi-Darbandi ◽  
Peter M. Gresshoff
Keyword(s):  
Coenzyme A ◽  
Nodule Development ◽  
Hmg Coa Reductase ◽  
Coa Reductase

scholarly journals The Role of the 3-Hydroxy 3-Methylglutaryl Coenzyme A Reductase Cytosolic Domain in Karmellae Biogenesis

1999 ◽  
Vol 10 (10) ◽  
pp. 3409-3423 ◽  
Author(s):  
Deborah A. Profant ◽  
Christopher J. Roberts ◽  
Ann J. Koning ◽  
Robin L. Wright
Keyword(s):  
Coenzyme A ◽  
Tertiary Structure ◽  
Catalytic Domain ◽  
Carboxyl Terminus ◽  
Membrane Domain ◽  
Hmg Coa Reductase ◽  
Cytosolic Domain ◽  
Coa Reductase ◽  
Er Membrane

In all cells examined, specific endoplasmic reticulum (ER) membrane arrays are induced in response to increased levels of the ER membrane protein 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase. In yeast, expression of Hmg1p, one of two yeast HMG-CoA reductase isozymes, induces assembly of nuclear-associated ER stacks called karmellae. Understanding the features of HMG-CoA reductase that signal karmellae biogenesis would provide useful insights into the regulation of membrane biogenesis. The HMG-CoA reductase protein consists of two domains, a multitopic membrane domain and a cytosolic catalytic domain. Previous studies had indicated that the HMG-CoA reductase membrane domain was exclusively responsible for generation of ER membrane proliferations. Surprisingly, we discovered that this conclusion was incorrect: sequences at the carboxyl terminus of HMG-CoA reductase can profoundly affect karmellae biogenesis. Specifically, truncations of Hmg1p that removed or shortened the carboxyl terminus were unable to induce karmellae assembly. This result indicated that the membrane domain of Hmg1p was not sufficient to signal for karmellae assembly. Using β-galactosidase fusions, we demonstrated that the carboxyl terminus was unlikely to simply serve as an oligomerization domain. Our working hypothesis is that a truncated or misfolded cytosolic domain prevents proper signaling for karmellae by interfering with the required tertiary structure of the membrane domain.

scholarly journals 3-Hydroxymethyl coenzyme A reductase inhibition attenuates spontaneous smooth muscle tone via RhoA/ROCK pathway regulated by RhoA prenylation

2010 ◽  
Vol 298 (6) ◽  
pp. G962-G969 ◽  
Author(s):  
Satish Rattan
Keyword(s):  
Smooth Muscle ◽  
Coenzyme A ◽  
Muscle Tone ◽  
Cholesterol Biosynthesis ◽  
Rho Kinase ◽  
Hmg Coa Reductase ◽  
Smooth Muscle Tone ◽  
Tonic Smooth Muscle ◽  
Coa Reductase

RhoA prenylation may play an important step in the translocation of RhoA in the basal internal anal sphincter (IAS) smooth muscle tone. Statins inhibit downstream posttranslational RhoA prenylation by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition (HMGCRI). The role of statins in relation to RhoA prenylation in the pathophysiology of the spontaneously tonic smooth muscle has not been investigated. In the present studies, we determined the effect of classical HMGCRI simvastatin on the basal IAS tone and RhoA prenylation and in the levels of RhoA/Rho kinase (ROCK) in the cytosolic vs. membrane fractions of the smooth muscle. Simvastatin produced concentration-dependent decrease in the IAS tone (via direct actions at the smooth muscle cells). The decrease in the IAS tone by simvastatin was associated with the decrease in the prenylation of RhoA, as well as RhoA/ROCK in the membrane fractions of the IAS, in the basal state. The inhibitory effects of the HMGCRI were completely reversible by geranylgeranyltransferase substrate geranylgeranyl pyrophosphate. Relaxation of the IAS smooth muscle via HMGCRI simvastatin is mediated via the downstream decrease in the levels of RhoA prenylation and ROCK activity. Studies support the concept that RhoA prenylation leading to RhoA/ROCK translocation followed by activation is important for the basal tone in the IAS. Data suggest that the role of HMG-CoA reductase may go beyond cholesterol biosynthesis, such as the regulation of the smooth muscle tone. The studies have important implications in the pathophysiological mechanisms and in the novel therapeutic approaches for anorectal motility disorders.

scholarly journals The role of N-linked glycosylation in the regulation of activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and proliferation of SV40-transformed 3T3 cells

1989 ◽  
Vol 260 (2) ◽  
pp. 597-600 ◽  
Author(s):  
O Larsson ◽  
W Engström
Keyword(s):  
Cell Proliferation ◽  
Dna Synthesis ◽  
Coenzyme A ◽  
Inhibitory Effects ◽  
3T3 Cells ◽  
Hmg Coa Reductase ◽  
Regulation Of Activity ◽  
Coa Reductase

The effects of glycosylation inhibitors on the proliferation of SV40-transformed 3T3 cells (SV-3T3) were examined in vitro. Whereas swainsonine and castanospermine, which inhibit distal steps in the glycosylational processing, exerted marginal or no effects on cell proliferation, a proximal inhibitor, tunicamycin, efficiently decreased the rate of DNA synthesis and also inhibited the activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase. The inhibitory effects of tunicamycin on cell proliferation could be partially reversed by addition of dolichol, a metabolite in the pathway regulated by HMG-CoA reductase. This finding suggests that tunicamycin exerts at least one of its effects on cell proliferation by modulating the activity of HMG-CoA reductase.

scholarly journals Chemical Phenotypes of the hmg1 and hmg2 Mutants of Arabidopsis Demonstrate the In-planta Role of HMG-CoA Reductase in Triterpene Biosynthesis

2007 ◽  
Vol 55 (10) ◽  
pp. 1518-1521 ◽  
Author(s):  
Kiyoshi Ohyama ◽  
Masashi Suzuki ◽  
Kazuo Masuda ◽  
Shigeo Yoshida ◽  
Toshiya Muranaka
Keyword(s):  
In Planta ◽  
Hmg Coa Reductase ◽  
Coa Reductase ◽  
Triterpene Biosynthesis

scholarly journals Dietary modification of the activation state of intestinal 3-hydroxy-3-methylglutaryl coenzyme a (HMG-CoA) reductase.

1984 ◽  
Vol 48 (11) ◽  
pp. 2745-2751
Author(s):  
Hirosuke OKU ◽  
Akira MORITA ◽  
Takashi IDE ◽  
Michihiro SUGANO
Keyword(s):  
Coenzyme A ◽  
Dietary Modification ◽  
Hmg Coa Reductase ◽  
Coa Reductase

scholarly journals An autonomous, but INSIG-modulated, role for the Sterol Sensing Domain in mallostery-regulated ERAD of yeast HMG-CoA reductase

2020 ◽  
pp. jbc.RA120.015910
Author(s):  
Margaret A Wangeline ◽  
Randolph Y Hampton
Keyword(s):  
Binding Site ◽  
Quaternary Structure ◽  
Limited Proteolysis ◽  
Hmg Coa Reductase ◽  
Coa Reductase ◽  
Level Analysis

HMG-CoA reductase (HMGR) undergoes feedback-regulated degradation as part of sterol pathway control. Degradation of the yeast HMGR isozyme Hmg2 is controlled by the sterol pathway intermediate GGPP, which causes misfolding of Hmg2, leading to degradation by the HRD pathway; we call this process mallostery. We evaluated the role of the Hmg2 sterol sensing domain (SSD) in mallostery, as well as the involvement of the highly conserved INSIG proteins. We show that the Hmg2 SSD is critical for regulated degradation of Hmg2 and required for mallosteric misfolding of GGPP as studied by in vitro limited proteolysis. The Hmg2 SSD functions independently of conserved yeast INSIG proteins, but its function was modulated by INSIG, thus imposing a second layer of control on Hmg2 regulation. Mutant analyses indicated that SSD-mediated mallostery occurred prior to and independent of HRD-dependent ubiquitination. GGPP-dependent misfolding was still extant but occurred at a much slower rate in the absence of a functional SSD, indicating that the SSD facilitates a physiologically useful rate of GGPP response, and implying that the SSD is not a binding site for GGPP. Non-functional SSD mutants allowed us to test the importance of Hmg2 quaternary structure in mallostery:  a non-responsive Hmg2 SSD mutant strongly suppressed regulation of a co-expressed, normal Hmg2. Finally, we have found that GGPP-regulated misfolding occurred in detergent-solubilized Hmg2, a feature that will allow next-level analysis of the mechanism of this novel tactic of ligand-regulated misfolding.

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