Inherited CalDAG-GEFI deficiency

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Presentation transcript:

Inherited CalDAG-GEFI deficiency by Marco Cattaneo Blood Volume 128(9):1165-1167 September 1, 2016 ©2016 by American Society of Hematology

Regulation of Rap1 activation by CalDAG-GEFI and RASA3. Regulation of Rap1 activation by CalDAG-GEFI and RASA3. Agonists binding to GPCRs of the Gq type or to ITAM-coupled receptors activate the PLC β or γ isoform to form IP3, which releases Ca2+ from stores. Ca2+ causes rapid CalDAG-GEFI–dependent Rap1 activation, which, through the cooperation of talin and kindlin-3, promotes the binding of adhesive proteins to αIIbβ3, enabling platelet aggregation. The process is regulated by RASA3, which hydrolyzes Rap1-GTP to inactive Rap-GDP. P2Y12, the GPCR of the Gi type that binds ADP, inactivates RASA3, allowing sustained Rap1 signaling and full platelet aggregation. Professional illustration created by Somersault18:24. Marco Cattaneo Blood 2016;128:1165-1167 ©2016 by American Society of Hematology