MT1-MMP is required for myeloid cell fusion via regulation of Rac1 signaling (Dev Cell, 2010, 18:77-89)

報告日期: 2011/04/19
報告時間: 16:00/16:50
報告學生: 謝銘育 (英文報告)
講評老師: 凌 斌

Full Text:

MT1-MMP Is Required for Myeloid Cell Fusion via Regulation of Rac1 Signaling
Pilar Gonzalo,1 Marta C. Guadamillas,1 Marı´a Victoria Herna´ ndez-Riquer,1 A´ ngela Polla´ n,1 Araceli Grande-Garcı´a,1 Rube´ n A. Bartolome´ ,2 Amit Vasanji,3 Chiara Ambrogio,4 Roberto Chiarle,4 Joaquı´n Teixido´ ,2 Juha Risteli,5 Suneel S. Apte,3 Miguel A. del Pozo,1 and Alicia G. Arroyo1,*
Developmental Cell18, 77–89,January 19, 2010
Speaker: Ming-Yu Hsieh (謝銘育)
Commentator: Dr. Ling, Pin (凌 斌老師)
Date: 2011/04/19 (pm 16:00-16:50)
Room: 602
BackgroundCell fusion is an important biological function and indispensable to the diffentiation of monocyte/macrophage (Mϕ) lineage. In the presence of inducers, Mϕ can differentiate into many cell types by cell fusion. One is the formation of osteoclast (OC) that controls bone remodeling and the other is giant cell (GC) that is associated with inflammation. Loss control of OC activity would cause serious diseases, like osteoporosis, Paget disease, osteopetrosis and bone metastasis for cancer cell. RANKL was found to be a key initiator of osteoclast differentiation. But the key regulator of Mϕ fusion is not well defined. MMPs (matrix metalloproteinases) participated in bone modeling and remodeling and among them, MT1-MMP (membrane type 1-MMP) is a membrane-anchored collagenase that plays important roles in the development of skeletal, lung, and adipose tissue. However, the role of MT1-MMP in Mϕ fusion has not been defined yet.
ObjectiveTo investigate the role of MT1-MMP in Mϕ fusion process.
ResultsThe author found that MT1-MMP is required for macrophage fusion during OC differentiation or GC formation. When MT1-MMP was knockout, bone marrow cells were defective for OC multinucleation or GC formation. And the OC progenitor cells displayed impaired motility and morphology. In addition, loss of MT1-MMP resulted in decreased Rac-1 activity. Further study indicated that the cytosolic tail of MT1-MMP could associate with p130Cas and affected motility and morphology of OC progenitor cell. Finally, the author indicated that MT1-MMP contributes to Mϕ fusion process probably via p130Cas interaction and the activation of Rac-1.
conclusionThis study identifies a new function of MT1-MMP in macrophage fusion process.

1.        Chun et al., (2006). A pericellular collagenase directs the 3-dimensional development of white adipose tissue. Cell 125, 577–591.
2.        Cui et al., (2007). CD200 and its receptor, CD200R, modulate bone mass via the differentiation of osteoclasts. Proc. Natl. Acad. Sci. USA 104, 14436–14441.