(571ai) Cis and Trans Interactions Can Compete In Heterotypic Adhesive Signaling | AIChE

(571ai) Cis and Trans Interactions Can Compete In Heterotypic Adhesive Signaling


Rodriquez, P. - Presenter, University of Pennsylvania
Discher, D. E. - Presenter, University of Pennsylvania
Subramanian, S. - Presenter, Merck & Co., Inc

Membrane protein-A on cell-A interacting with membrane protein-B on cell-B is the usual 'trans' interaction in cell-cell adhesion, but if cell-A also expresses protein-B, then 'cis' interactions might also compete. The Marker of Self adhesion protein CD47 is found on all cell types and binds SIRPa on Macrophages in trans at sub-microMolar affinities, but human Macrophages also express CD47 and competition in cis proves significant. Binding of CD47 in trans inhibits phagocytosis of a CD47-displaying target [Tsai and Discher, JCB 2008], and we find here that knockdown of CD47 on Macrophages is shown to lead to greater binding of soluble CD47 and, separately, enhanced phagocytosis of opsonized targets. The effective Kd for binding in trans depends linearly on cis CD47 on the macrophage, consistent with the simplest competition model. Additionally, CHO cells engineered to express CD47-GFP bind more soluble SIRPa than CHO cells displaying both CD47 and SIRPa, although high affinity antibodies can out-compete cis interactions. Both Hematopoietic and Mesenchymal Stem Cells also express both CD47 and SIRPa, and inhibitory cis interactions on these cells are also clear. The fact that Macrophages need the Marker of Self CD47 seems to make cis interactions unavoidable, and any other cell type that expresses both proteins will require accounting for this intrinsic cis competition.