Capelluto Research Group

Capelluto Research Group (2018)

Our current research centers on the molecular structure and biochemical functions of signaling transduction systems involved in membrane trafficking and cell signaling. Our goal is to understand how protein domains transduce and modulate signals from biological membranes.

Adaptor Proteins in Endosomal Protein Trafficking

Ubiquitylation is a highly controlled post-translational modification of proteins, in which proteins are conjugated either with monoubiquitin or polyubiquitin chains. Ubiquitin modifications on target proteins are recognized by ubiquitin-binding domains, which are found in several effector proteins. We study the function and structure of the Toll-interacting protein (Tollip), which contains the C2 and CUE ubiquitin-binding domains and participates in the innate immune signaling pathway and endosomal protein trafficking.

Lipid-binding Events in the Wnt Signaling Pathway

The Wnt-dependent, b-catenin-independent pathway modulates cell movement and behavior. A downstream regulator of this signaling pathway is Dishevelled (Dvl), which among other multiple interactions, binds to the Frizzled receptor and the plasma membrane via phosphatidic acid (PA) in a mechanism proposed to be pH dependent. We defined the structural and functional basis of PA recognition by the Dvl2 DEP domain. We also established that PA binding by the Dvl2 DEP domain is pH-dependent and resembles the mechanism of PA deprotonation.

Modulators of Platelet Aggregation

Platelets form a clump at the site of vascular injury to stop bleeding. One negative regulator of platelet aggregation is Disabled-2 (Dab2), a protein released to the extracellular surface upon platelet activation. Dab2 inhibits platelet aggregation by competing with fibrinogen for alphaIIb-beta3 integrin receptor binding. The inhibitory role of Dab2 depends on its recognition to sulfatides, sphingolipids found on the platelet surface, which interact with coagulation proteins, playing a major role in haemostasis.

Lab Members

Name
Title

Annan, Nhyira

Visiting Student

Brantly, Nataliya

Visitor

Gouletas, Fofi

Visiting Student

Littleton, Evan

Visiting Student

Reddy, Neha

Visiting Student

Song, Wei

Visiting Student

Tang, Tuo-Xian

Visiting Student

Wallace, Robert

Visiting Student

Xion, Wen

Visiting Student