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Ginsberg, M.

Publications and source records attributed to Ginsberg, M..

2 recordsLinked to original sources

Endothelial struts, a mechanism to generate large lumenized blood vessels de novo

Lumenization of de novo formed blood vessels occurs either through cell hollowing (intracellular lumen)1-3 or cord hollowing (extracellular lumen)4-6 and restricts thereby the initial lumen diameter to one or two endothelial cells (ECs) respectively. However, vasculogenesis can result in large diameter blood vessels, raising the question how these vessels are formed. Here, we describe an alternative model of vasculogenesis that results in the formation of large diameter vessels. In this model, ECs coalesce into a branched network of EC struts within the future lumen of the vessel. These struts maintain the patency of the vessel and serve as a scaffold for the ECs forming the vessel wall, which initially consists out of a few patches of ECs. Together, we show that endothelial struts facilitate the formation of large blood vessels without being bound by the prerequisite of a cord-like structure, nor are they restricted in size.

developmental biology

A Rap1 binding site and lipid-dependent helix in talin F1 domain cooperate in integrin activation

Rap1 GTPases bind effectors, such as RIAM, to enable talin1 to induce integrin activation. In addition, Rap1 binds directly to the talin1 F0 domain (F0); however, this interaction makes a negligible contribution to integrin activation in CHO cells or platelets. Here, we show that talin1 F1 domain contains a previously undetected Rap1 binding site of similar affinity to that in F0. A structure-guided point mutant (R118E) in F1, which blocks Rap1 binding, abolishes the capacity of Rap1 to potentiate talin1-induced integrin activation. The capacity of F1 to mediate Rap1-dependent integrin activation depends on a unique loop in F1 that transforms into an amphipathic helix upon binding to membrane lipids. Basic membrane-facing residues of this helix are critical as charge reversal mutations led to dramatic suppression of talin1-dependent activation. Thus, a novel Rap1 binding site and a lipid-dependent amphipathic helix in talin1 F1 cooperate to enable a direct Rap1-talin1 interaction to cause integrin activation.\n\nSummaryThis work reveals that Rap1 GTPases bind directly to talin1 F1 domain and by cooperating with a unique lipid-dependent amphipathic helix in the F1 domain effects talin1-mediated integrin activation.

cell biology