scholarly journals Human HINT1 Mutant Proteins that Cause Axonal Motor Neuropathy Exhibit Anomalous Interactions with Partner Proteins

2021 ◽  
Author(s):  
Elsa Cortés-Montero ◽  
María Rodríguez-Muñoz ◽  
Pilar Sánchez-Blázquez ◽  
Javier Garzón-Niño
Keyword(s):  
Motor Neuropathy ◽  
Mutant Proteins ◽  
Partner Proteins

scholarly journals Human HINT1 Mutant Proteins that Cause Axonal Motor Neuropathy Exhibit Anomalous Interactions with Partner Proteins

2020 ◽  
Author(s):  
Elsa Cortés-Montero ◽  
María Rodríguez-Muñoz ◽  
Pilar Sánchez-Blázquez ◽  
Javier Garzón-Niño
Keyword(s):  
G Protein ◽  
Motor Neurons ◽  
Axonal Neuropathy ◽  
Normal Function ◽  
Motor Neuropathy ◽  
Protein Signaling ◽  
Mutant Proteins ◽  
Human Motor ◽  
G Protein Coupled ◽  
Partner Proteins

Abstract The 14 kDa histidine triad nucleotide-binding protein 1 (HINT1) is critical to maintain the normal function of motor neurons. Thus, a series of human HINT1 mutants cause autosomal recessive axonal neuropathy with neuromyotonia. HINT1 establishes a series of regulatory interactions with signaling proteins, some of which are enriched in motor neurons, such as the type 1 sigma receptor or intracellular domain (ICD) of transmembrane teneurin 1, both of which are also implicated in motor disturbances. In a previous study, we reported the capacity of HINT1 to remove the small ubiquitin-like modifier (SUMO) from a series of substrates and the influence of HINT1 mutants on this activity. We now report how human HINT1 mutations affect the interaction of HINT1 with the regulator of its SUMOylase activity, calcium-activated calmodulin, and its substrate SUMO. Moreover, HINT1 mutants exhibited anomalous interactions with G-protein coupled receptors, such as the mu-opioid, and with glutamate N-methyl-D-aspartate receptors as well. Additionally, these HINT1 mutants showed impaired associations with transcriptional regulators such as the regulator of G protein signaling Z2 protein and the cleaved N-terminal ICD of teneurin 1. Thus, the altered SUMOylase activity of human HINT1 mutants and their anomalous interactions with partner proteins may disrupt signaling pathways essential to the normal function of human motor neurons.

Motor neuropathy and alacrima: oligosymptomatic triple A syndrome

2006 ◽  
Vol 37 (03) ◽  
Author(s):  
K Brockmann ◽  
K Koehler ◽  
M Krumbholz ◽  
J Gärtner ◽  
A Hübner
Keyword(s):  
Motor Neuropathy ◽  
Triple A Syndrome

Changes in the muscles of mastication before and after primary stereotactic radiosurgery in patients with idiopathic trigeminal neuralgia

2019 ◽  
pp. 1-8 ◽  
Author(s):  
Nasser Mohammed ◽  
Yi-Chieh Hung ◽  
Thomas J. Eluvathingal Muttikkal ◽  
Roy C. Bliley ◽  
Zhiyuan Xu ◽  
...  
Keyword(s):  
Trigeminal Neuralgia ◽  
Muscle Atrophy ◽  
Motor Neuropathy ◽  
Significant Pain ◽  
Medial Pterygoid ◽  
Before And After ◽  
Pterygoid Muscles ◽  
Masseter Muscles ◽  
Muscles Of Mastication ◽  
New Onset

OBJECTIVEThe motor root of the trigeminal nerve runs close to the sensory root and receives considerable radiation during Gamma Knife radiosurgery (GKRS) for trigeminal neuralgia (TN). The object of this study was to evaluate via MRI the changes in the muscles of mastication before and after upfront GKRS in patients with idiopathic TN.METHODSIn this single-institution retrospective cohort study, all patients with idiopathic unilateral TN treated with primary GKRS at the University of Virginia in the period from 2007 to 2017 were included provided that they had pre- and post-GKRS MRI data. The thicknesses of the temporalis, pterygoid, and masseter muscles were measured on both pre- and post-GKRS MRI in a blinded fashion. Changes in the muscles like fatty infiltration, MRI signal, or atrophy were noted.RESULTSAmong the 68 patients eligible for inclusion in the study, 136 temporalis muscles, 136 medial pterygoid muscles, 136 lateral pterygoid muscles, and 136 masseter muscles were assessed. A subset of patients was found to have muscle atrophy even prior to GKRS. Pre-GKRS atrophy of the masseter, medial pterygoid, lateral pterygoid, and temporalis muscles was seen in 18 (26%), 16 (24%), 9 (13%), and 16 (24%) patients, respectively. Logistic regression analysis showed that distribution of pain in the V3 territory (p = 0.01, OR 5.43, 95% CI 1.46–20.12) and significant pain on chewing (p = 0.02, OR 5.32, 95% CI 1.25–22.48) were predictive of pre-GKRS atrophy. Reversal of atrophy of these muscles occurred after GKRS in a majority of the patients. The incidence of new-onset permanent post-GKRS muscle atrophy was 1.5%. The median follow-up was 39 months (range 6–108 months).CONCLUSIONSA subset of patients with TN with significant pain on chewing have pre-GKRS disuse atrophy of the muscles of mastication. A reversal of the atrophy occurs in a majority of the patients following GKRS. New-onset motor neuropathy post-GKRS was rare.

The Proteins Interacting with Prmt5 in Medaka (Oryzias latipes) Identified by Yeast Two-Hybridization

2020 ◽  
Vol 27 (10) ◽  
pp. 971-978
Author(s):  
Hao Shen ◽  
Xiaosha Zhang ◽  
Md. Abdullah Al Hafiz ◽  
Xiaoting Liang ◽  
Qiting Yao ◽  
...  
Keyword(s):  
Nadh Dehydrogenase ◽  
Binding Proteins ◽  
Zinc Fingers ◽  
Regulation Of Gene Expression ◽  
Apolipoprotein A ◽  
Cell Growth And Differentiation ◽  
Pr Domain ◽  
Partner Proteins ◽  
Apo Ai ◽  
Model Fish

Background: Prmt5 plays major role in regulation of gene expression, RNA processing, cell growth and differentiation, signal transduction, germ cell development, etc., in mammals. Prmt5 is also related to cancer. Knowing the proteins interacting with Prmt5 is important to understand Prmt5’s function in cells. Although there have been reports on proteins binding with Prmt5 in mammals, the partner proteins of Prmt5 in fish are still unclear. Objectives: The objective was to obtain proteins that bind with Prmt5 in medaka, a model fish. Methods: Yeast two hybridization was adopted to achieve the objective. Medaka Prmt5 was used as a bait to fish the prey, binding proteins in a cDNA library of medaka. Co-immunoprecipitation and in silicon analysis were performed to study the interaction of medaka Mep50 and Prmt5. Results: Eight proteins were identified to bind with Prmt5 from 69 preliminary positive colonies. The binding proteins are methylosome protein 50 (Mep50), apolipoprotein A-I-like (Apo-AI), PR domain containing protein 1a with zinc fingers (Prdm1a), Prdm1b, T-cell immunoglobulin mucin family member 3 (Tim-3), phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthase (Paics), NADH dehydrogenase subunit 4 (ND4) and sciellin (Scl). Co-immunoprecipitation confirmed the interaction of medaka Prmt5 and Mep50. Predicted structures of medaka Prtm5 and Mep50 are similar to that of human PRMT5 and MEP50. Conclusion: Medaka Mep50, Prdm1a, Prdm1b, Apo-AI, Tim-3, Paics, ND4, and Scl bind with Prmt5.

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