Migrasome biogenesis: when biochemistry meets biophysics on membranes.

The migrasome, an organelle recently discovered in migrating cells, facilitates intercellular communication and plays crucial roles in various physiological and pathological conditions. The formation of migrasomes is governed by a tightly regulated process that progresses through three distinct stages: nucleation, maturation, and expansion. This process is regulated by essential molecules such as sphingomyelin lsynthase 2 (SMS2), phosphatidylinositol-4-phosphate 5-kinase type I α (PIP5K1α), integrins, and tetraspanins. The formation of migrasomes is propelled by the assembly of membrane microdomains, driven by the dynamic interaction between biochemical reactions and the physical properties of the membrane at migrasome formation sites. Migrasomes, newly identified organelles, play crucial roles in intercellular communication, contributing to organ development and angiogenesis. These vesicles, forming on retraction fibers of migrating cells, showcase a sophisticated architecture. Recent research reveals that migrasome biogenesis is a complicated and highly regulated process. This review summarizes the mechanisms governing migrasome formation, proposing a model in which biogenesis is understood through the lens of membrane microdomain assembly. It underscores the critical interplay between biochemistry and biophysics. The biogenesis unfolds in three distinct stages: nucleation, maturation, and expansion, each characterized by unique morphological, biochemical, and biophysical features. We also explore the broader implications of migrasome research in membrane biology and outline key unanswered questions that represent important directions for future investigation. [ABSTRACT FROM AUTHOR]