scholarly journals Biophysical Analysis of Kindlin-3 Reveals an Elongated Conformation and Maps Integrin Binding to the Membrane-distal β-Subunit NPXY Motif

2012 ◽  
Vol 287 (45) ◽  
pp. 37715-37731 ◽  
Author(s):  
Luke A. Yates ◽  
Anna K. Füzéry ◽  
Roman Bonet ◽  
Iain D. Campbell ◽  
Robert J. C. Gilbert
Keyword(s):  
Β Subunit ◽  
Biophysical Analysis ◽  
Npxy Motif

scholarly journals Regulation of Integrin Affinity States through an NPXY Motif in the β Subunit Cytoplasmic Domain

1995 ◽  
Vol 270 (15) ◽  
pp. 8553-8558 ◽  
Author(s):  
Timothy E. O'Toole ◽  
Jari Ylanne ◽  
Brian M. Culley
Keyword(s):  
Cytoplasmic Domain ◽  
Β Subunit ◽  
Npxy Motif

Isolated integrin β3 subunit cytoplasmic domains require membrane anchorage and the NPXY motif to recruit to adhesion complexes but do not discriminate between β1– and β3-positive complexes

2005 ◽  
Vol 94 (07) ◽  
pp. 155-166 ◽  
Author(s):  
Lionel Ponsonnet ◽  
Alessandro Foletti ◽  
Gian Carlo Alghisi ◽  
Curzio Rüegg
Keyword(s):  
Endothelial Cells ◽  
Transmembrane Domain ◽  
Focal Adhesions ◽  
Cytoplasmic Domain ◽  
Β Subunit ◽  
Cytoplasmic Domains ◽  
Npxy Motif ◽  
Covalently Linked ◽  
Focal Structures ◽  
Adhesion Complex

SummaryIntegrin adhesion receptors consist of non-covalently linked α and β subunits each of which contains a large extracellular domain, a single transmembrane domain and a short cytoplasmic tail. Engaged integrins recruit to focal structures globally termed adhesion complexes. The cytoplasmic domain of the β subunit is essential for this clustering. β1 and β3 integrins can recruit at distinct cellular locations (i.e. fibrillar adhesions vs focal adhesions, respectively) but it is not clear whether individual β subunit cytoplasmic and transmembrane domains are by themselves sufficient to drive orthotopic targeting to the cognate adhesion complex. To address this question, we expressed fulllength β3 transmembrane anchored cytoplasmic domains and truncated β3 cytoplasmic domains as GFP-fusion constructs and monitored their localization in endothelial cells. Membrane-anchored full-length β3 cytoplasmic domain and a β3 mutant lacking the NXXY motif recruited to adhesion complexes, while β3 mutants lacking the NPXY and NXXY motifs or the transmembrane domain did not. Replacing the natural β subunit transmembrane domain with an unrelated (i.e. HLA-A2 α chain) transmembrane domain significantly reduced recruitment to adhesion complexes. Transmembrane anchored β3 and cytoplasmic domain constructs, however, recruited without discrimination to β1– and β3-rich adhesions complexes. These findings demonstrate that membrane anchorage and the NPXY (but not the NXXY) motif are necessary for β3 cytoplasmic domain recruitment to adhesion complexes and that the natural transmembrane domain actively contributes to this recruitment. The β3 transmembrane and cytoplasmic domains alone are insufficient for orthotopic recruitment to cognate adhesion complexes.

scholarly journals Identification of Integrin β Subunit Mutations that Alter Heterodimer Function In Situ

2004 ◽  
Vol 15 (8) ◽  
pp. 3829-3840 ◽  
Author(s):  
Alison L. Jannuzi ◽  
Thomas A. Bunch ◽  
Robert F. West ◽  
Danny L. Brower
Keyword(s):  
Integrin Subunit ◽  
Β Subunit ◽  
Negative Effects ◽  
Gene Encoding ◽  
Structural Domains ◽  
Conserved Residues ◽  
Animal Development ◽  
Open Conformation ◽  
Npxy Motif

We conducted a genetic screen for mutations in myospheroid, the gene encoding the Drosophila βPS integrin subunit, and identified point mutants in all of the structural domains of the protein. Surprisingly, we find that mutations in very strongly conserved residues will often allow sufficient integrin function to support the development of adult animals, including mutations in the ADMIDAS site and in a cytoplasmic NPXY motif. Many mutations in the I-like domain reduce integrin expression specifically when βPS is combined with activating αPS2 cytoplasmic mutations, indicating that integrins in the extended conformation are unstable relative to the inactive, bent heterodimers. Interestingly, the screen has identified alleles that show gain-of-function characteristics in cell culture, but have negative effects on animal development or viability. This is illustrated by the allele mysb58; available structural models suggest that the molecular lesion of mysb58, V409>D, should promote the “open” conformation of the β subunit I-like domain. This expectation is supported by the finding that αPS2βPS (V409>D) promotes adhesion and spreading of S2 cells more effectively than does wild-type αPS2βPS, even when βPS is paired with αPS2 containing activating cytoplasmic mutations. Finally, comparisons with the sequence of human β8 suggest that evolution has targeted the “mysb58” residue as a means of affecting integrin activity.

The chorionic gonadotropin β-subunit gene is controlled by Pitx1 and Egr1

2007 ◽  
Vol 115 (S 1) ◽  
Author(s):  
A Henke ◽  
M Simoni ◽  
E Nieschlag ◽  
J Gromoll
Keyword(s):  
Chorionic Gonadotropin ◽  
Β Subunit ◽  
Subunit Gene

Cloning and Analyzing of G-protein β-Subunit Gene in Rhizoctonia solani Causing Soybean Sharp Eyespot

2009 ◽  
Vol 35 (2) ◽  
pp. 370-374
Author(s):  
Bing-Tian MA ◽  
Guang-Lin QU ◽  
Wen-Juan HUANG ◽  
Yu-Fan LIN ◽  
Shi-Gui LI
Keyword(s):  
Rhizoctonia Solani ◽  
G Protein ◽  
Β Subunit ◽  
Subunit Gene ◽  
Sharp Eyespot

Individual and Combined Assessment of Ser680Asn FSH Receptor and FSHβ -211 G>T Gene Polymorphisms in Ovarian Response in IVF/ICSI Program

2020 ◽  
Vol 21 ◽  
Author(s):  
Elli Anagnostou ◽  
Alexia Kafkoutsou ◽  
Despina Mavrogianni ◽  
Ekaterini Domali ◽  
Evangelia Dimitroulia ◽  
...  
Keyword(s):  
Gene Polymorphism ◽  
Gene Polymorphisms ◽  
Ovarian Response ◽  
Greek Population ◽  
Control Group ◽  
Genotype Distribution ◽  
Β Subunit ◽  
Molecular Genetic Study ◽  
The Impact ◽  
First Time

Background: Molecular biology tools, such as the detection of single nucleotide polymorphisms (SNPs), have been considered to assist to the management of the ovarian stimulation protocols. Purpose: The aim of this study was to evaluate the impact of two polymorphisms, the Asn680Ser polymorphism of the FSHR gene, and the FSH β subunit (FSHβ) gene polymorphism -211 G>T, in a Greek population of women undergoing IVF/ICSI program in our center. In addition, a control group of fertile women was studied, to verify whether there are differences in the genotype distribution between fertile and infertile population for both polymorphisms, as the FSHβ gene polymorphism -211 G>T is studied for the first time in the Greek population. Results : The FSH β-211 G>T polymorphism, studied for the first time in the Greek infertile population, appears to be quite rare. When studying the two polymorphisms separately, statistically significant differences were obtained that concerned the LH levels. Discussion: According to the combination analysis of the two polymorphisms by the number of alleles, women with 2-3 polymorphic alleles needed more days of stimulation, but there were no differences in pregnancy rates. Conclusion: This molecular genetic study helps to elucidate whether the polygenic combination of the Asn680Ser and FSH β subunit -211 G>T gene polymorphisms is of additive value in the prediction of ovarian response to exogenous gonadotropins.

Abnormal neurodevelopment outcome in case of neonatal hyperekplexia secondary to missense mutation in GLRB gene

2020 ◽  
Vol 13 (12) ◽  
pp. e236152
Author(s):  
Naveen Parkash Gupta ◽  
Vinita Verma ◽  
Saurabh Chopra ◽  
Vivek Choudhury
Keyword(s):  
Genetic Testing ◽  
Missense Mutation ◽  
Genetic Predisposition ◽  
Seizure Disorder ◽  
Β Subunit ◽  
Tonic Spasm ◽  
Initial Improvement ◽  
External Stimuli ◽  
Neurodevelopment Outcome

Hyperekplexia is an exaggerated startle to external stimuli associated with a generalised increase in tone seen in neonates with both sporadic and genetic predisposition. This is an uncommon neurological entity that is misdiagnosed as seizure. A 28-days-old infant was admitted to us with characteristic intermittent generalised tonic spasm being treated as a seizure disorder. The infant had characteristic stiffening episode, exaggerated startle and non-habituation on tapping the nose. Hyperekplexia was suspected and confirmed by genetic testing (mutation in the β subunit of glycine was found). Initial improvement was seen with the use of clonazepam, which was not sustained. At the age of 4.5 years, the child is still having neurobehavioural issues like hyperactivity and sensory hyper-responsiveness. Usually, hyperekplexia is benign in nature. We report a case of hyperekplexia with non-sense mutation in the β subunit of GlyR gene having abnormal neurodevelopmental findings at 4.5 years.

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