scholarly journals Characterizing the VAC14 multimeric state

2021 ◽  
Author(s):  
Shannon Cheuk Ying Ho
Keyword(s):  
Nervous System ◽  
Membrane Trafficking ◽  
Adaptor Protein ◽  
Lipid Kinase ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Cellular Processes ◽  
Lipid Phosphatase ◽  
Lateral Sclerosis ◽  
Tooth Disease

PtdIns(3,5)₂ is involved in a number of cellular processes, such as the regulation of endolysosome morphology and membrane trafficking, autophagy and ion transport. In mammala, PtdIns(3,5)₂ deficiency results in vacuolation most notable in the neurons of the central and peripheral nervous system. This can potentially block the trafficking of neurotransmitters leading to a progression of neurodegeneration diseases such as amyotrophic lateral sclerosis and Charcot-Marie-Tooth disease. PtdIns(3,5)₂ is synthesized by the Fab1/PIKfyve lipid kinase and degraded by the Fig4/Sac3 lipid phosphatase. Fab1 and Fig4 are found in a complex with its regulator, the Fac14/ArPIKfyve adaptor protein. The aim of this study was to identify the multimeric state of recombinant Vac14 in order to help elucidate the importance of the Vac14 multimer in the regulation of PtdIns(3,5)₂. The result of this study indicated that recombinant Vac14 forms a homodimer and/or homotrimer.

scholarly journals Characterizing the VAC14 multimeric state

2021 ◽  
Author(s):  
Shannon Cheuk Ying Ho
Keyword(s):  
Nervous System ◽  
Membrane Trafficking ◽  
Adaptor Protein ◽  
Lipid Kinase ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Cellular Processes ◽  
Lipid Phosphatase ◽  
Lateral Sclerosis ◽  
Tooth Disease

PtdIns(3,5)₂ is involved in a number of cellular processes, such as the regulation of endolysosome morphology and membrane trafficking, autophagy and ion transport. In mammala, PtdIns(3,5)₂ deficiency results in vacuolation most notable in the neurons of the central and peripheral nervous system. This can potentially block the trafficking of neurotransmitters leading to a progression of neurodegeneration diseases such as amyotrophic lateral sclerosis and Charcot-Marie-Tooth disease. PtdIns(3,5)₂ is synthesized by the Fab1/PIKfyve lipid kinase and degraded by the Fig4/Sac3 lipid phosphatase. Fab1 and Fig4 are found in a complex with its regulator, the Fac14/ArPIKfyve adaptor protein. The aim of this study was to identify the multimeric state of recombinant Vac14 in order to help elucidate the importance of the Vac14 multimer in the regulation of PtdIns(3,5)₂. The result of this study indicated that recombinant Vac14 forms a homodimer and/or homotrimer.

scholarly journals Characterization of the Regulation and Function of Phosphatidylinositol 3,5-Bisphosphate

2021 ◽  
Author(s):  
Shannon Cheuk Ying Ho
Keyword(s):  
Membrane Trafficking ◽  
Adaptor Protein ◽  
Cellular Functions ◽  
Lipid Kinase ◽  
Cellular Processes ◽  
Lipid Phosphatase ◽  
Tooth Type ◽  
And Function ◽  
Endocytic Compartments ◽  
Lysosomal Acidification

PtdIns(3,5)P2 is a low abundance phosphoinositide that is involved in a variety of cellular processes. Most notably, PtdIns(3,5)P2 is known to regulate vacuolar/lysosomal morphology. Deficiency in PtdIns(3,5)P2 results in enlargement of the yeast vacuole and, an extensive vacuolation of the late endocytic compartments in higher eukaryotes (1, 2). In addition, PtdIns(3,5)P2 is also involved in cellular functions including membrane trafficking, autophagy, and vacuolar/lysosomal acidification. However, the current study provided evidence that shows that the vacuole/lysosomes of PtdIns(3,5)P2-deficient cells remain acidic. Hence, PtdIns(3,5)P2 may not have a role in steady-state vacuolar/lysosomal acidification. PtdIns(3,5)P2 is synthesized by the Fab1 lipid kinase and degraded by the antagonistic Fig4 lipid phosphatase. Vac14, an adaptor protein, is known to interact with both Fab1 and Fig4 to form a complex on the vacuolar membrane. This study demonstrated that Vac14 is required to form a homodimer for its interaction with Fig4 and Fab1. In addition, formation of the homodimer is necessary for regulation of PtdIns(3,5)P2. Mutations in human Vac14 and Fig4 has been identified in patients with neurodegenerative diseases, such as amyotrophic lateral sclerosis and Charcot-Marie-Tooth Type 4J (3, 4). This study provides an important stepping stone in characterizing the regulatory mechanism and understanding the function of PtdIns(3,5)P2

scholarly journals Characterization of the Regulation and Function of Phosphatidylinositol 3,5-Bisphosphate

2021 ◽  
Author(s):  
Shannon Cheuk Ying Ho
Keyword(s):  
Membrane Trafficking ◽  
Adaptor Protein ◽  
Cellular Functions ◽  
Lipid Kinase ◽  
Cellular Processes ◽  
Lipid Phosphatase ◽  
Tooth Type ◽  
And Function ◽  
Endocytic Compartments ◽  
Lysosomal Acidification

PtdIns(3,5)P2 is a low abundance phosphoinositide that is involved in a variety of cellular processes. Most notably, PtdIns(3,5)P2 is known to regulate vacuolar/lysosomal morphology. Deficiency in PtdIns(3,5)P2 results in enlargement of the yeast vacuole and, an extensive vacuolation of the late endocytic compartments in higher eukaryotes (1, 2). In addition, PtdIns(3,5)P2 is also involved in cellular functions including membrane trafficking, autophagy, and vacuolar/lysosomal acidification. However, the current study provided evidence that shows that the vacuole/lysosomes of PtdIns(3,5)P2-deficient cells remain acidic. Hence, PtdIns(3,5)P2 may not have a role in steady-state vacuolar/lysosomal acidification. PtdIns(3,5)P2 is synthesized by the Fab1 lipid kinase and degraded by the antagonistic Fig4 lipid phosphatase. Vac14, an adaptor protein, is known to interact with both Fab1 and Fig4 to form a complex on the vacuolar membrane. This study demonstrated that Vac14 is required to form a homodimer for its interaction with Fig4 and Fab1. In addition, formation of the homodimer is necessary for regulation of PtdIns(3,5)P2. Mutations in human Vac14 and Fig4 has been identified in patients with neurodegenerative diseases, such as amyotrophic lateral sclerosis and Charcot-Marie-Tooth Type 4J (3, 4). This study provides an important stepping stone in characterizing the regulatory mechanism and understanding the function of PtdIns(3,5)P2

scholarly journals Relapsing Remitting Multiple Sclerosis in X-Linked Charcot-Marie-Tooth Disease with Central Nervous System Involvement

2015 ◽  
Vol 2015 ◽  
pp. 1-3 ◽  
Author(s):  
Georgios Koutsis ◽  
Georgia Karadima ◽  
Paraskewi Floroskoufi ◽  
Maria Raftopoulou ◽  
Marios Panas
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Brain Mri ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Tooth Disease

We report a patient with relapsing remitting multiple sclerosis (MS) and X-linked Charcot-Marie-Tooth disease (CMTX), carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr) which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS) involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars). Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis.

scholarly journals Genotype-Phenotype Correlations in Charcot-Marie-Tooth Disease Due to MTMR2 Mutations and Implications in Membrane Trafficking

2019 ◽  
Vol 13 ◽  
Author(s):  
Haicui Wang ◽  
Ayşe Kaçar Bayram ◽  
Rosanne Sprute ◽  
Ozkan Ozdemir ◽  
Emily Cooper ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease
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