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Platelet Rubicon Bidirectional Regulation of GPVI and Integrin αIIbβ3 Signaling Mitigates Stroke Infarction Without
Xiaoyan Chen1,2, Jingke Li1,2, Yangyang Liu3
1Department of Pathology and Pathophysiology and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|January 22, 2026
Summary
Researchers found that the autophagic protein Rubicon is crucial for preventing stroke and brain hemorrhage. Targeting Rubicon
Area of Science:
- Biochemistry
- Cell Biology
- Neuroscience
Background:
- Platelet receptors glycoprotein VI (GPVI) and integrin αIIbβ3 play critical roles in thrombosis and hemostasis.
- Targeting GPVI is a potential strategy for cerebral ischemia-reperfusion injury (CIRI) therapy, but underlying mechanisms are unclear.
- Autophagy and its regulatory proteins, like Rubicon, are increasingly recognized for their roles in platelet function and vascular diseases.
Purpose of the Study:
- To elucidate the cellular mechanism of Rubicon in platelet function and its role in cerebral ischemia-reperfusion injury (CIRI).
- To investigate the interaction of Rubicon with Bruton's tyrosine kinase (Btk) and its impact on GPVI and αIIbβ3 signaling.
- To evaluate the therapeutic potential of targeting the Rubicon-Btk pathway for CIRI treatment.
Main Methods:
- Generated megakaryocyte-platelet-specific Rubicon-deficient mice.
- Investigated the interaction between Rubicon and Btk using co-immunoprecipitation and other biochemical assays.
- Assessed thrombus formation and stability in vitro and in vivo.
- Evaluated cerebral infarction volume and hemorrhage in mouse models of stroke.
- Measured Rubicon expression in platelets from patients with acute ischemic-reperfusion injury.
Main Results:
- Megakaryocyte-platelet-specific deficiency of Rubicon accelerated stroke and exacerbated cerebral hemorrhage.
- Rubicon interacts with Btk to inhibit GPVI-mediated thrombus formation.
- Rubicon prevents αIIbβ3-mediated selective autophagy and Btk degradation, stabilizing platelet thrombi.
- Rubicon expression is decreased in platelets of patients with acute ischemic-reperfusion injury.
- A peptide mimicking the Rubicon-Btk interaction significantly reduced cerebral infarction volume in mice.
Conclusions:
- Rubicon plays a critical, previously unrecognized role in regulating platelet function and mitigating cerebral ischemia-reperfusion injury.
- The Rubicon-Btk interaction is a key regulator of both GPVI and αIIbβ3 signaling pathways in platelets.
- Rubicon is dispensable for hemostasis but crucial during the reperfusion phase of CIRI.
- Peptide-based therapeutics mimicking Rubicon's function represent a promising, selective, and safe strategy for treating CIRI.
Keywords:
Rubicon (Run domain protein as Beclin‐1 interacting and cysteine‐rich containing)cerebral ischemia‐reperfusion injuryglycoprotein VIintegrin αIIbβ3More Related Videos
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