Title : A novel mechanism of thrombocytopenia by PS exposure through TMEM16F in sphingomyelin synthase 1 deficiency.

Pub. Date : 2021 Oct 26

PMID : 34478523






14 Functional Relationships(s)
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Compound Name
Protein Name
Organism
1 Sphingomyelin synthase 1 (SMS1) contributes to the generation of membrane sphingomyelin (SM) and affects SM-mediated physiological functions. Sphingomyelins sphingomyelin synthase 1 Mus musculus
2 Sphingomyelin synthase 1 (SMS1) contributes to the generation of membrane sphingomyelin (SM) and affects SM-mediated physiological functions. Sphingomyelins sphingomyelin synthase 1 Mus musculus
3 Sphingomyelin synthase 1 (SMS1) contributes to the generation of membrane sphingomyelin (SM) and affects SM-mediated physiological functions. Sphingomyelins sphingomyelin synthase 1 Mus musculus
4 Sphingomyelin synthase 1 (SMS1) contributes to the generation of membrane sphingomyelin (SM) and affects SM-mediated physiological functions. Sphingomyelins sphingomyelin synthase 1 Mus musculus
5 Sphingomyelin synthase 1 (SMS1) contributes to the generation of membrane sphingomyelin (SM) and affects SM-mediated physiological functions. Sphingomyelins sphingomyelin synthase 1 Mus musculus
6 Sphingomyelin synthase 1 (SMS1) contributes to the generation of membrane sphingomyelin (SM) and affects SM-mediated physiological functions. Sphingomyelins sphingomyelin synthase 1 Mus musculus
7 Deficiency of SMS1, but not SMS2, prevented SM production and enhanced phosphatidylserine (PS) externalization on the plasma membranes of platelets and megakaryocytes. Sphingomyelins sphingomyelin synthase 1 Mus musculus
8 Deficiency of SMS1, but not SMS2, prevented SM production and enhanced phosphatidylserine (PS) externalization on the plasma membranes of platelets and megakaryocytes. Phosphatidylserines sphingomyelin synthase 1 Mus musculus
9 Deficiency of SMS1, but not SMS2, prevented SM production and enhanced phosphatidylserine (PS) externalization on the plasma membranes of platelets and megakaryocytes. Phosphatidylserines sphingomyelin synthase 1 Mus musculus
10 Multimer formation in the plasma membrane of TMEM16F, a known calcium (Ca2+)-activated nonselective ion channel and Ca2+-dependent PS scramblase, was enhanced, resulting in PS externalization to outer-leaflets through increased Ca2+ influx in immortalized mouse embryonic fibroblasts established from SMS1-KO mice (SMS1-KO tMEFs), as seen with SMS1-KO platelets. Calcium sphingomyelin synthase 1 Mus musculus
11 Multimer formation in the plasma membrane of TMEM16F, a known calcium (Ca2+)-activated nonselective ion channel and Ca2+-dependent PS scramblase, was enhanced, resulting in PS externalization to outer-leaflets through increased Ca2+ influx in immortalized mouse embryonic fibroblasts established from SMS1-KO mice (SMS1-KO tMEFs), as seen with SMS1-KO platelets. Calcium sphingomyelin synthase 1 Mus musculus
12 SMS1-KO tMEFs in which TMEM16F was knocked out using the CRISPR-Cas9 system lacked both the Ca2+ influx and excess PS exposure seen in SMS1-KO tMEFs. Phosphatidylserines sphingomyelin synthase 1 Mus musculus
13 Therefore, SM depletion on platelet membrane microdomains due to SMS1 deficiency enhanced PS externalization via a Ca2+ influx through TMEM16F activation, leading to elevated platelet clearance and causing hemostasis dysfunction through thrombocytopenia. Sphingomyelins sphingomyelin synthase 1 Mus musculus
14 Therefore, SM depletion on platelet membrane microdomains due to SMS1 deficiency enhanced PS externalization via a Ca2+ influx through TMEM16F activation, leading to elevated platelet clearance and causing hemostasis dysfunction through thrombocytopenia. Phosphatidylserines sphingomyelin synthase 1 Mus musculus