Synaptotagmins （Syts） are a large family of integral membrane proteins that regulate synaptic function and membrane traffcking. Emerging evidences show involvement of Syts in human diseases. Here, we review the rece...Synaptotagmins （Syts） are a large family of integral membrane proteins that regulate synaptic function and membrane traffcking. Emerging evidences show involvement of Syts in human diseases. Here, we review the recent studies of several Syts （Syt1, 2, 7, 11, and 14） in the pathophysiological mechanisms of neurodegeneration disorders such as Alzheimer’s disease, Parkinson’s disease, and attention-defcit/hyperactivity disorder etc. A better understanding of the diverse physiological and pathological functions of different Syt isoforms is needed for potential therapeutic interventions in the future.展开更多
BACKGROUND Synaptotagmins(SYTs)are a family of 17 membrane transporters that function as calcium ion sensors during the release of Ca2+-dependent neurotransmitters and hormones.However,few studies have reported whethe...BACKGROUND Synaptotagmins(SYTs)are a family of 17 membrane transporters that function as calcium ion sensors during the release of Ca2+-dependent neurotransmitters and hormones.However,few studies have reported whether members of the SYT family play a role in glucose uptake in diabetic retinopathy(DR)through Ca2+/glucose transporter-1(GLUT1)and the possible regulatory mechanism of SYTs.AIM To elucidate the role of the SYT family in the regulation of glucose transport in retinal pigment epithelial cells and explore its potential as a therapeutic target for the clinical management of DR.METHODS DR was induced by streptozotocin in C57BL/6J mice and by high glucose medium in human retinal pigment epithelial cells(ARPE-19).Bioinformatics analysis,reverse transcriptase-polymerase chain reaction,Western blot,flow cytometry,ELISA,HE staining,and TUNEL staining were used for analysis.RESULTS Six differentially expressed proteins(SYT2,SYT3,SYT4,SYT7,SYT11,and SYT13)were found between the DR and control groups,and SYT4 was highly expressed.Hyperglycemia induces SYT4 overexpression,manipulates Ca2+influx to induce GLUT1 fusion with the plasma membrane,promotes abnormal expression of the glucose transporter GLUT1 and excessive glucose uptake,induces ARPE-19 cell apoptosis,and promotes DR progression.Parkin deficiency inhibits the proteasomal degradation of SYT4 in DR,resulting in SYT4 accumulation and enhanced GLUT1 fusion with the plasma membrane,and these effects were blocked by oe-Parkin treatment.Moreover,dysregulation of the myelin transcription factor 1(Myt1)-induced transcription of SYT4 in DR further activated the SYT4-mediated stimulus-secretion coupling process,and this process was inhibited in the oe-MYT1-treated group.CONCLUSION Our study reveals the key role of SYT4 in regulating glucose transport in retinal pigment epithelial cells during the pathogenesis of DR and the underlying mechanism and suggests potential therapeutic targets for clinical DR.展开更多
The WNK kinases are a recently discovered family of serine-threonine kinases that have been shown to play an essential role in the regulation of electrolyte homeostasis. Intronic deletions in the WNK1 gene result in i...The WNK kinases are a recently discovered family of serine-threonine kinases that have been shown to play an essential role in the regulation of electrolyte homeostasis. Intronic deletions in the WNK1 gene result in its overexpression and lead to pseudohypoaldosteronism type II, a disease with salt-sensitive hypertension and hyperkalemia. This review focuses on the recent evidence elucidating the structure of the kinase domain of WNK1 and functions of these kinases in normal and disease physiology. Their functions have implications for understanding the biochemical mechanism that could lead to the retention or insertion of proteins in the plasma membrane. The WNK kinases may be able to influence ion homeostasis through its effects on synaptotagmin function.展开更多
基金The author was supported by grants from the Beijing Natural Science Foundation Program and the Scientifc Research Key Program of Beijing Municipal Commission of Education （KZ201510025023）, the National Natural Science Foundation of China （31471085）.
文摘Synaptotagmins （Syts） are a large family of integral membrane proteins that regulate synaptic function and membrane traffcking. Emerging evidences show involvement of Syts in human diseases. Here, we review the recent studies of several Syts （Syt1, 2, 7, 11, and 14） in the pathophysiological mechanisms of neurodegeneration disorders such as Alzheimer’s disease, Parkinson’s disease, and attention-defcit/hyperactivity disorder etc. A better understanding of the diverse physiological and pathological functions of different Syt isoforms is needed for potential therapeutic interventions in the future.
文摘BACKGROUND Synaptotagmins(SYTs)are a family of 17 membrane transporters that function as calcium ion sensors during the release of Ca2+-dependent neurotransmitters and hormones.However,few studies have reported whether members of the SYT family play a role in glucose uptake in diabetic retinopathy(DR)through Ca2+/glucose transporter-1(GLUT1)and the possible regulatory mechanism of SYTs.AIM To elucidate the role of the SYT family in the regulation of glucose transport in retinal pigment epithelial cells and explore its potential as a therapeutic target for the clinical management of DR.METHODS DR was induced by streptozotocin in C57BL/6J mice and by high glucose medium in human retinal pigment epithelial cells(ARPE-19).Bioinformatics analysis,reverse transcriptase-polymerase chain reaction,Western blot,flow cytometry,ELISA,HE staining,and TUNEL staining were used for analysis.RESULTS Six differentially expressed proteins(SYT2,SYT3,SYT4,SYT7,SYT11,and SYT13)were found between the DR and control groups,and SYT4 was highly expressed.Hyperglycemia induces SYT4 overexpression,manipulates Ca2+influx to induce GLUT1 fusion with the plasma membrane,promotes abnormal expression of the glucose transporter GLUT1 and excessive glucose uptake,induces ARPE-19 cell apoptosis,and promotes DR progression.Parkin deficiency inhibits the proteasomal degradation of SYT4 in DR,resulting in SYT4 accumulation and enhanced GLUT1 fusion with the plasma membrane,and these effects were blocked by oe-Parkin treatment.Moreover,dysregulation of the myelin transcription factor 1(Myt1)-induced transcription of SYT4 in DR further activated the SYT4-mediated stimulus-secretion coupling process,and this process was inhibited in the oe-MYT1-treated group.CONCLUSION Our study reveals the key role of SYT4 in regulating glucose transport in retinal pigment epithelial cells during the pathogenesis of DR and the underlying mechanism and suggests potential therapeutic targets for clinical DR.
文摘The WNK kinases are a recently discovered family of serine-threonine kinases that have been shown to play an essential role in the regulation of electrolyte homeostasis. Intronic deletions in the WNK1 gene result in its overexpression and lead to pseudohypoaldosteronism type II, a disease with salt-sensitive hypertension and hyperkalemia. This review focuses on the recent evidence elucidating the structure of the kinase domain of WNK1 and functions of these kinases in normal and disease physiology. Their functions have implications for understanding the biochemical mechanism that could lead to the retention or insertion of proteins in the plasma membrane. The WNK kinases may be able to influence ion homeostasis through its effects on synaptotagmin function.
