Dissection of autophagy in human platelets.
Continuous turnover of intracellular components by autophagy is necessary to preserve cellular homeostasis in all tissues. Despite recent advances in identifying autophagy-related genes and understanding the functions of autophagy in developmental and pathological conditions, so far, the role of autophagy in platelet, a specific anucleate cell type, is poorly understood. In this study, we showed that human platelets express the autophagy-related proteins ATG5, ATG7, and LC3. The same as in nucleated mammalian cells, autophagy was stimulated by cell starvation or the MTOR inhibitor rapamycin in a phosphatidylinositol 3-kinase (PtdIns3K)-dependent manner. Disruption of autophagic flux led to impairment of platelet aggregation and adhesion. Furthermore, Becn1 heterozygous knockout mice displayed a prolonged bleeding time and reduced platelet aggregation. These results suggest a potential role of autophagy in the regulation of platelet function, and imply that gene transcription may not be an essential prerequisite for adaptive autophagy.
Department of Biochemistry and Molecular Biology; Program in Molecular and Cell Biology; Zhejiang University School of Medicine; Hangzhou, China.
Wenfeng
W
Feng
Department of Biochemistry and Molecular Biology; Program in Molecular and Cell Biology; Zhejiang University School of Medicine; Hangzhou, China.
Chunmei
C
Chang
Department of Pathology and Pathophysiology; Zhejiang University School of Medicine; Hangzhou, China.
Dongjiao
D
Luo
Department of Biochemistry and Molecular Biology; Program in Molecular and Cell Biology; Zhejiang University School of Medicine; Hangzhou, China.
Hua
H
Su
Department of Pathology and Pathophysiology; Zhejiang University School of Medicine; Hangzhou, China.
Shanshan
S
Yu
Department of Respiratory Medicine; Second Affiliated Hospital; Zhejiang University School of Medicine; Hangzhou, China.
Wen
W
Hua
Department of Respiratory Medicine; Second Affiliated Hospital; Zhejiang University School of Medicine; Hangzhou, China.
Zhihua
Z
Chen
Department of Pathology and Pathophysiology; Zhejiang University School of Medicine; Hangzhou, China.
Hu
H
Hu
Department of Biochemistry and Molecular Biology; Program in Molecular and Cell Biology; Zhejiang University School of Medicine; Hangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease; First Affiliated Hospital; Zhejiang University School of Medicine; Hangzhou, China.
Wei
W
Liu
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1; D001760:Bleeding Time; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D006579:Heterozygote; D006801:Humans; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D019869:Phosphatidylinositol 3-Kinases; D058570:TOR Serine-Threonine Kinases; C115010:Becn1 protein, mouse
Beclin 1; autophagosome; autophagy; platelet; thrombus