scholarly journals Rough endoplasmic reticulum trafficking errors by different classes of mutant dentin sialophosphoprotein (DSPP) cause dominant negative effects in both dentinogenesis imperfecta and dentin dysplasia by entrapping normal DSPP

2012 ◽  
Vol 27 (6) ◽  
pp. 1309-1321 ◽  
Author(s):  
Zofia von Marschall ◽  
Seeun Mok ◽  
Matthew D Phillips ◽  
Dianalee A McKnight ◽  
Larry W Fisher
Keyword(s):  
Endoplasmic Reticulum ◽  
Rough Endoplasmic Reticulum ◽  
Dominant Negative ◽  
Dentinogenesis Imperfecta ◽  
Negative Effects ◽  
Dentin Sialophosphoprotein

scholarly journals Revisiting PC1/3 Mutants: Dominant-Negative Effect of Endoplasmic Reticulum-Retained Mutants

Endocrinology ◽  
2015 ◽  
Vol 156 (10) ◽  
pp. 3625-3637 ◽  
Author(s):  
Elias H. Blanco ◽  
Bruno Ramos-Molina ◽  
Iris Lindberg
Keyword(s):  
Endoplasmic Reticulum ◽  
Peptide Hormone ◽  
Biochemical Properties ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Wild Type ◽  
Negative Effects ◽  
Hormone Synthesis ◽  
Type Protein ◽  
Wild Type Protein

Prohormone convertase 1/3 (PC1/3), encoded by the gene PCSK1, is critical for peptide hormone synthesis. An increasing number of studies have shown that inactivating mutations in PCSK1 are correlated with endocrine pathologies ranging from intestinal dysfunction to morbid obesity, whereas the common nonsynonymous polymorphisms rs6232 (N221D) and rs6234–rs6235 (Q665E-S690T) are highly associated with obesity risk. In this report, we revisited the biochemical and cellular properties of PC1/3 variants in the context of a wild-type PC1/3 background instead of the S357G hypermorph background used for all previous studies. In the wild-type background the PC1/3 N221D variant exhibited 30% lower enzymatic activity in a fluorogenic assay than wild-type PC1/3; this inhibition was greater than that detected in an equivalent experiment using the PC1/3 S357G background. A PC1/3 variant with the linked carboxyl-terminal polymorphisms Q665E-S690T did not show this difference. We also analyzed the biochemical properties of 2 PC1/3 mutants, G209R and G593R, which are retained in the endoplasmic reticulum (ER), and studied their effects on wild-type PC1/3. The expression of ER-retained mutants induced ER stress markers and also resulted in dominant-negative blockade of wild-type PC1/3 prodomain cleavage and decreased expression of wild-type PC1/3, suggesting facilitation of the entry of wild-type protein to a degradative proteasomal pathway. Dominant-negative effects of PC1/3 mutations on the expression and maturation of wild-type protein, with consequential effects on PC1/3 availability, add a new element which must be considered in population and clinical studies of this gene.

Modification of Pineal Ultrastructure by Exogenous Hormones

1967 ◽  
Vol 25 ◽  
pp. 170-171
Author(s):  
R. A. Turner ◽  
A. E. Rodin ◽  
D. K. Roberts
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Rough Endoplasmic Reticulum ◽  
Estradiol Benzoate ◽  
Female Rats ◽  
List Type ◽  
Type Number ◽  
Pregnant Rats ◽  
Gonadal Atrophy ◽  
Pineal Ultrastructure

There have been many reports which establish a relationship between the pineal and sexual structures, including gonadal hypertrophy after pinealectomy, and gonadal atrophy after injection of pineal homogenates or of melatonin. In order to further delineate this relationship the pineals from 5 groups of female rats were studied by electron microscopy:ControlsPregnant ratsAfter 4 weekly injections of 0.1 mg. estradiol benzoate.After 8 daily injections of 150 mcgm. melatonin (pineal hormone).After 8 daily injections of 3 mg. serotonin (melatonin precursor).No ultrastructural differences were evident between the control, and the pregnancy and melatonin groups. However, the estradiol injected animals exhibited a marked increase in the amount and size of rough endoplasmic reticulum within the pineal cells.

Membrane-associated microtubular areays induced in proximal myelinated processes of dorsal root ganglia by large doses of vitamin B6

1986 ◽  
Vol 44 ◽  
pp. 368-369
Author(s):  
V.J. Montpetit ◽  
S. Dancea ◽  
L. Tryphonas ◽  
D.F. Clapin
Keyword(s):  
Animal Model ◽  
Endoplasmic Reticulum ◽  
Dorsal Root Ganglia ◽  
Rough Endoplasmic Reticulum ◽  
Dorsal Root ◽  
Vitamin B6 ◽  
Morphological Changes ◽  
Model System ◽  
Sensory Nerves ◽  
Peripheral Sensory

Very large doses of pyridoxine (vitamin B6) are neurotoxic in humans, selectively affecting the peripheral sensory nerves. We have undertaken a study of the morphological and biochemical aspects of pyridoxine neurotoxicity in an animal model system. Early morphological changes in dorsal root ganglia (DRG) associated with pyridoxine megadoses include proliferation of neurofilaments, ribosomes, rough endoplasmic reticulum, and Golgi complexes. We present in this report evidence of the formation of unique aggregates of microtubules and membranes in the proximal processes of DRG which are induced by high levels of pyridoxine.

scholarly journals Glucocorticoid Receptor β (GRβ): Beyond Its Dominant-Negative Function

2021 ◽  
Vol 22 (7) ◽  
pp. 3649
Author(s):  
Patricia Ramos-Ramírez ◽  
Omar Tliba
Keyword(s):  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Cell Communication ◽  
Cell Types ◽  
The Body ◽  
Dominant Negative ◽  
Negative Effects ◽  
Independent Manner ◽  
Distinct Cell ◽  
Induced Apoptosis

Glucocorticoids (GCs) act via the GC receptor (GR), a receptor ubiquitously expressed in the body where it drives a broad spectrum of responses within distinct cell types and tissues, which vary in strength and specificity. The variability of GR-mediated cell responses is further extended by the existence of GR isoforms, such as GRα and GRβ, generated through alternative splicing mechanisms. While GRα is the classic receptor responsible for GC actions, GRβ has been implicated in the impairment of GRα-mediated activities. Interestingly, in contrast to the popular belief that GRβ actions are restricted to its dominant-negative effects on GRα-mediated responses, GRβ has been shown to have intrinsic activities and “directly” regulates a plethora of genes related to inflammatory process, cell communication, migration, and malignancy, each in a GRα-independent manner. Furthermore, GRβ has been associated with increased cell migration, growth, and reduced sensitivity to GC-induced apoptosis. We will summarize the current knowledge of GRβ-mediated responses, with a focus on the GRα-independent/intrinsic effects of GRβ and the associated non-canonical signaling pathways. Where appropriate, potential links to airway inflammatory diseases will be highlighted.

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