Platelets: covert regulators of lymphatic development.
The field of platelet biology has rapidly expanded beyond the classical role of platelets in preventing blood loss and orchestrating clot formation. Despite the lack of transcriptional ability of these anuclear cell fragments, platelet function is now thought to encompass such diverse contexts as tissue repair, immune activation, primary tumor formation, and metastasis. Recent studies from multiple groups have turned the spotlight on an exciting new role for platelets in the formation of lymphatic vessels during embryonic development. Genetic experiments demonstrate that podoplanin, a transmembrane protein expressed on lymphatic endothelial cells, engages the platelet C-type lectin-like receptor 2 (CLEC-2) when exposed to blood, leading to SYK-SLP-76-dependent platelet activation. When components of this pathway are disrupted, aberrant vascular connections form, resulting in blood-lymphatic mixing. Furthermore, platelet-null embryos manifest identical blood-lymphatic mixing. The identification of platelets as the critical cell type mediating blood-lymphatic vascular separation raises new questions in our understanding of lymphatic development and platelet biology.
Department of Medicine and Cardiovascular Institute, University of Pennsylvania, Philadelphia Pa 19104, USA.
Cara C
CC
Bertozzi
Paul R
PR
Hess
Mark L
ML
Kahn
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000196:embryology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D015539:Platelet Activation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D000072377:Syk Kinase; D000098853:Podoplanin
D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C529518:CLEC-2 protein, mouse; C490441:Pdpn protein, mouse; D000098853:Podoplanin; C092947:SLP-76 signal Transducing adaptor proteins; C000606896:SYK protein, human; C000606897:Syk protein, mouse