scholarly journals Drosophila Mon1 and Rab7 interact to regulate glutamate receptor levels at the neuromuscular junction

2020 ◽  
Vol 64 (4-5-6) ◽  
pp. 289-297
Author(s):  
Anagha Basargekar ◽  
Shweta Yogi ◽  
Zeeshan Mushtaq ◽  
Senthilkumar Deivasigamani ◽  
Vimlesh Kumar ◽  
...  
Keyword(s):  
Neuromuscular Junction ◽  
Glutamate Receptor ◽  
Receptor Expression ◽  
Strong Increase ◽  
Short Life Span ◽  
Early Endosomes ◽  
Severe Motor ◽  
Strength And Plasticity ◽  
Larval Neuromuscular Junction

Regulation of post-synaptic receptors plays an important role in determining synaptic strength and plasticity. The Drosophila larval neuromuscular junction (nmj) has been used extensively as a model to understand some of these processes. In this context, we are interested in the role of Drosophila Monensin sensitivity protein 1 (DMon1) in regulating glutamate receptor (GluRIIA) levels at the nmj. DMon1 is an evolutionarily conserved protein which, in complex with calcium caffeine zinc sensitivity1 (CCZ1), regulates the conversion of early endosomes to late endosomes through recruitment of Rab7. C-terminal deletion mutants of Dmon1 (Dmon1Δ181) exhibit lethality. The escapers have a short life span and exhibit severe motor defects. At the nmj, these mutants show defects in synaptic morphology and a strong increase in GluRIIA levels. The mechanism by which Dmon1 regulates GluRIIA is unclear. In this study, we have characterized an EMS mutant referred to as pog 1 and demonstrate it to be an allele of Dmon1. Further, we have examined the role of rab7 in regulating GluRIIA. We show that similar to Dmon1, knock-down of rab7 using RNAi in neurons, but not muscles, leads to an increase in GluRIIA. Loss of one copy each of Dmon1 and rab7 leads to a synergistic increase in receptor expression. Further, overexpression of an activated Rab7 can rescue the GluRIIA phenotype observed in Dmon1Δ181 mutants. Together, these results highlight a neuronal role for Rab7 in GluRIIA regulation and underscore the importance of the endo-lysosomal pathway in this process.

scholarly journals Dmon1 and rab7 interact to regulate glutamate receptor GluRIIA levels at the larval Drosophila neuromuscular junction

2020 ◽  
Author(s):  
Anagha Basargekar ◽  
Shweta Yogi ◽  
Zeeshan Mushtaq ◽  
Senthil Deivasigamani ◽  
Vimlesh Kumar ◽  
...  
Keyword(s):  
Neuromuscular Junction ◽  
Glutamate Receptor ◽  
Receptor Expression ◽  
Strong Increase ◽  
Short Life Span ◽  
Early Endosomes ◽  
Severe Motor ◽  
Strength And Plasticity ◽  
Larval Neuromuscular Junction

AbstractRegulation of post-synaptic receptors plays an important role in determining synaptic strength and plasticity. The Drosophila larval neuromuscular junction (nmj) has been used extensively as a model to understand some of these processes. In this context, we are interested in the role of Drosophila Monensin sensitive protein 1 (DMon1) in regulating glutamate receptor (GluRIIA) levels at the nmj. Dmon1 is an evolutionarily conserved protein which, in complex with CCZ1, regulates the conversion of early endosomes to late endosomes through recruitment of Rab7. C-terminal deletion mutants of Dmon1 (Dmon1Δ181) exhibit lethality. The escapers have a short life span and exhibit severe motor defects. At the nmj, these mutants show a defects in synaptic morphology and a strong increase in glutamate receptor GluRIIA levels. The mechanism by which Dmon1 regulates GluRIIA is unclear.In this study, we have described the characterization the mutation in an EMS mutant referred to as pog1 and demonstrate this mutant to be an allele of Dmon1. Further, we have examined the role of rab7 in regulation the of GluRIIA. We show that similar to Dmon1, knock-down of rab7 using RNAi in neurons, and not muscles, leads to an increase in GluRIIA. Loss of one copy each of Dmon1 with rab7 leads to a synergistic increase in receptor expression. Further, overexpression of an activated Rab7 can rescue the GluRIIA phenotype observed in Dmon1Δ181 mutants. Together, these results highlight a neuronal role for Rab7 in GluRIIA regulation and underscores the important of the endo-lysosomal pathway in this process.

scholarly journals Lola regulates glutamate receptor expression at the Drosophila neuromuscular junction

Biology Open ◽  
2012 ◽  
Vol 1 (4) ◽  
pp. 362-375 ◽  
Author(s):  
A. Fukui ◽  
M. Inaki ◽  
G. Tonoe ◽  
H. Hamatani ◽  
M. Homma ◽  
...  
Keyword(s):  
Neuromuscular Junction ◽  
Glutamate Receptor ◽  
Receptor Expression

Role of the 807 C/T Polymorphism of the α2 Gene in Platelet GP Ia Collagen Receptor Expression and Function

1999 ◽  
Vol 81 (06) ◽  
pp. 951-956 ◽  
Author(s):  
J. Corral ◽  
R. González-Conejero ◽  
J. Rivera ◽  
F. Ortuño ◽  
P. Aparicio ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Cell Types ◽  
Receptor Expression ◽  
Case Control Studies ◽  
Platelet Surface ◽  
Vitro Analysis ◽  
And Function ◽  
In Vitro Analysis

SummaryThe variability of the platelet GP Ia/IIa density has been associated with the 807 C/T polymorphism (Phe 224) of the GP Ia gene in American Caucasian population. We have investigated the genotype and allelic frequencies of this polymorphism in Spanish Caucasians. The T allele was found in 35% of the 284 blood donors analyzed. We confirmed in 159 healthy subjects a significant association between the 807 C/T polymorphism and the platelet GP Ia density. The T allele correlated with high number of GP Ia molecules on platelet surface. In addition, we observed a similar association of this polymorphism with the expression of this protein in other blood cell types. The platelet responsiveness to collagen was determined by “in vitro” analysis of the platelet activation and aggregation response. We found no significant differences in these functional platelet parameters according to the 807 C/T genotype. Finally, results from 3 case/control studies involving 302 consecutive patients (101 with coronary heart disease, 104 with cerebrovascular disease and 97 with deep venous thrombosis) determined that the 807 C/T polymorphism of the GP Ia gene does not represent a risk factor for arterial or venous thrombosis.

scholarly journals Modulation of Macrophages M1/M2 Polarization Using Carbohydrate-Functionalized Polymeric Nanoparticles

Polymers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 88
Author(s):  
Raquel G. D. Andrade ◽  
Bruno Reis ◽  
Benjamin Costas ◽  
Sofia A. Costa Lima ◽  
Salette Reis
Keyword(s):  
Inflammatory Responses ◽  
Polymeric Nanoparticles ◽  
Interaction Mechanism ◽  
Mannose Receptor ◽  
The Body ◽  
Receptor Expression ◽  
Production Methods ◽  
Polymeric Nanocarriers ◽  
Efficient Delivery

Exploiting surface endocytosis receptors using carbohydrate-conjugated nanocarriers brings outstanding approaches to an efficient delivery towards a specific target. Macrophages are cells of innate immunity found throughout the body. Plasticity of macrophages is evidenced by alterations in phenotypic polarization in response to stimuli, and is associated with changes in effector molecules, receptor expression, and cytokine profile. M1-polarized macrophages are involved in pro-inflammatory responses while M2 macrophages are capable of anti-inflammatory response and tissue repair. Modulation of macrophages’ activation state is an effective approach for several disease therapies, mediated by carbohydrate-coated nanocarriers. In this review, polymeric nanocarriers targeting macrophages are described in terms of production methods and conjugation strategies, highlighting the role of mannose receptor in the polarization of macrophages, and targeting approaches for infectious diseases, cancer immunotherapy, and prevention. Translation of this nanomedicine approach still requires further elucidation of the interaction mechanism between nanocarriers and macrophages towards clinical applications.

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