迁移体的研究进展

Advancements in migrasome biology

迁移体是近年来发现和命名的一种新型膜结构,在细胞间通讯中发挥着至关重要的作用.迁移体由迁移性细胞产生,并通过收缩丝与细胞胞体相连接.迁移体广泛地存在于多种细胞、组织和器官中,其内部富含信号和生物活性分子,在一系列生理和病理过程中扮演着关键角色.本综述详细概述了迁移体生物学研究的最新进展,涵盖了迁移体形成的分子机制、重要的生物学功能及其在各种疾病中的关联和潜在的应用.此外,本综述分享了对迁移体生物学未来发展方向的一些思考和看法,提出了该研究领域面临的新兴挑战和一系列未解决的关键问题.

Migrasomes are newly identified organelles that play a significant role in cell-cell communication.Originating from migrating cells,they develop on retraction fibers.Migrasomes are prevalent across various cells,tissues,and organs and are enriched with signaling molecules and bioactive substances that are critical to numerous physiological and pathological processes.In the decade since their initial discovery,researchers have systematically explored the molecular mechanisms underlying migrasome formation and their biological functions.This review summarizes the most recent findings in migrasome research,including the molecular mechanisms of migrasome biogenesis,their physiological roles,associations with various diseases,and potential applications.Migrasome formation is a complex process that unfolds in three distinct phases:nucleation,maturation,and expansion,each characterized by unique morphological,biochemical,and biophysical features:(1)the nucleation phase begins with the assembly of sphingomyelin synthase 2(SMS2)foci,which form stationary focal points on the basal membrane at the leading edges of migrating cells.SMS2 catalyzes the conversion of ceramide to sphingomyelin,thereby delineating the sites of migrasome formation and promoting their growth from these focal points.(2)The maturation phase,is marked by the synthesis of phosphatidylinositol 4,5-bisphosphate[PI(4,5)P2],facilitated by phosphatidylinositol 4-monophosphate 5-kinases(PIP5Ks).PI(4,5)P2 interacts with Rab35,which in turn recruits integrin-α5 to the migrasome formation site.These interactions are pivotal for migrasome maturation.The maturation of the migrasome formation site,characterized by integrin recruitment,signaling the commencement of the migrasome expansion phase.(3)The expansion phase.Initially,the swelling of migrasomes at the formation site is triggered by changes in tension,which is then followed by a stabilization stage.This stabilization involves the assembly of tetraspanin-enriched microdomains(TEMs)from the retraction fiber into larger macrodomains,known as micrometerscale tetraspanin macrodomains(TEMAs).These TEMAs then swell into the vesicle-like structure that is characteristic of migrasomes.Migrasomes have been identified as pivotal in a multitude of biological processes.They regulate embryonic organ morphogenesis and angiogenesis by delivering chemokines or growth factors to specific areas,providing regional signals that facilitate long-distance cell-cell communication during embryonic development.Additionally,migrasomes facilitate the transfer of materials,such as mRNA,between neighboring cells,thus mediating short-distance cell-cell communication.Furthermore,migrasomes contribute to cellular homeostasis by expelling damaged mitochondria from the cell.Recent findings have unveiled a unique and localized method of secretion in migrating cells,suggesting that migrasomes serve as a principal secretion route.Moreover,studies have uncovered neutrophil-derived migrasomes as a previously unrecognized essential component of the hemostasis system,circulating in the bloodstream and rich in adhesion molecules and coagulation factors,which aid in clot formation at injury sites.Currently,migrasomes are gaining recognition for their potential as a significant mechanism for intercellular communication.However,the field is replete with unanswered questions that range from mechanistic understanding to physiological significance.These unresolved questions will undoubtedly shape the future trajectory of this burgeoning field.The review offers insights into future directions in migrasome biology,discussing emerging challenges and highlighting key unresolved issues in the field.