The Mechanism Study Of Migrasome Formation

When cells migrate,the long fibrillar structures leaved behind are retraction fibers where small vesicls grow up,we called these vesicles migrasome.The diameter of migrasomes is about 1-2?m,and there are some small vesicles in the mgirasome.The formation of migrasome is migration dependent.The cytosolic contents can be transported into migrasomes and released to the outside this process which we name “migracytosis”.Migrasome may play important roles in cell-cell communication.We found that migrasome sticks to the matrix when the retraction fibers breaks,which indicating the existence of molecules that may hold the migrasome on the matrix,we found that integrin ?5?1 is enriched on the migrasome.We also found the integrin on the migrasome is in an activated state,and the 3D distribution of integrin is major on the bottom side of migrasome.The emergence of integrin on migrasome is much earlier than TSPAN4,and we predict that integrin-extracellular matrix(ECM)interaction is one of the earliest events of migrasome formation.Compared with focal adhesion which is the most well known integrin enriched structure,we found migrasome is different in protein composition,structure and lifetime.Integrins are major receptors for ECM,and different ECM has different integrin receptors.We knocked down the fibronectin receptor-integrin ?5,and found that migrasome formation was dramatically decreased on fibronection while no obvious effect on other ECMs.We overexpressed integrin ?3,and found migrasome formation is increased on its ligand laminin511.When we overexpressed integrin ?1,migrasome foramation is visibly increased on its ligand collagen IV while no obvious change on other ECMs.In summary,we found the pairing of integrin and ECM dertermines migrasome formation.Placenta is one important organ in fetal development.It links the mother and the fetus.In the development of human placenta,there is an invasive cell type called extravillious trophoblasts(EVT)on the tips of villus.We found that the purified EVT can produce migrasome in vitro and we also seen migrasome like structure in the ultrathin section of a placenta tissue by transmission electron microscope(TEM).The migrasome of EVT can be marked by the EVT specific marker integrin ?5 and HLA-G,and the chemokine CXCL12 is enriched in migrasome which we believe may play a role in cell-cell communication.In order to further understand placenta and avoid ethic limitation,we transfer our system to the mice.We found glycogen trophoblast(GlyTs)which is also invasive in the mouse placenta,and purified GlyTs can produce migrasome in vitro.And we also observed migrasome like structure in the ultrathin section of mosue placenta tissue by TEM.