| First Author | Leatherdale A | Year | 2021 |
| Journal | J Thromb Haemost | Volume | 19 |
| Issue | 2 | Pages | 547-561 |
| PubMed ID | 33179420 | Mgi Jnum | J:307643 |
| Mgi Id | MGI:6721260 | Doi | 10.1111/jth.15171 |
| Citation | Leatherdale A, et al. (2021) Multimerin 1 supports platelet function in vivo and binds to specific GPAGPOGPX motifs in fibrillar collagens that enhance platelet adhesion. J Thromb Haemost 19(2):547-561 |
| abstractText | BACKGROUND: Multimerin 1 (human: MMRN1, mouse: Mmrn1) is a homopolymeric, adhesive, platelet and endothelial protein that binds to von Willebrand factor and enhances platelet adhesion to fibrillar collagen ex vivo. OBJECTIVES: To examine the impact of Mmrn1 deficiency on platelet adhesive function, and the molecular motifs in fibrillar collagen that bind MMRN1 to enhance platelet adhesion. METHODS: Mmrn1-deficient mice were generated and assessed for altered platelet adhesive function. Collagen Toolkit peptides, and other triple-helical collagen peptides, were used to identify multimerin 1 binding motifs and their contribution to platelet adhesion. RESULTS: MMRN1 bound to conserved GPAGPOGPX sequences in collagens I, II, and III (including GPAGPOGPI, GPAGPOGPV, and GPAGPOGPQ) that enhanced activated human platelet adhesion to collagen synergistically with other triple-helical collagen peptides (P < .05). Mmrn1(-/-) and Mmrn1(+/-) mice were viable and fertile, with complete and partial platelet Mmrn1 deficiency, respectively. Relative to wild-type mice, Mmrn1(-/-) and Mmrn1(+/-) mice did not have overt bleeding, increased median bleeding times, or increased wound blood loss (P >/= .07); however, they both showed significantly impaired platelet adhesion and thrombus formation in the ferric chloride injury model (P </= .0003). Mmrn1(-/-) platelets had impaired adhesion to GPAGPOGPX peptides and fibrillar collagen (P </= .03) and formed smaller aggregates than wild-type platelets when captured onto collagen, triple-helical collagen mimetic peptides, von Willebrand factor, or fibrinogen (P </= .008), despite preserved, low shear, and high shear aggregation responses. CONCLUSIONS: Multimerin 1 supports platelet adhesion and thrombus formation and binds to highly conserved, GPAGPOGPX motifs in fibrillar collagens that synergistically enhance platelet adhesion. |
