Migrasomes are recently discovered vesicle-like structures on retraction fibers of migrating cells that have been linked with transfer of cellular contents, shedding of unwanted materials, and information integration. However, whether and how the cell migration paradigm regulates migrasome formation is not clear. Here, we report that there are significantly fewer migrasomes in turning cells compared with straight persistently migrating cells. The major insight underlying this observation is that as the cells elongate, their rear ends become narrower, subsequently resulting in fewer retraction fibers during impersistent migration. In addition to migration persistence, we reveal that migration speed positively corelates with migrasome formation, owing to the derived length of retraction fibers. Substantiating our hypothesis, genetically removing vimentin compromises cell migration speed and persistence and leads to fewer migrasomes. Together, our data explicate the critical roles of two cell migration patterns, persistence and speed, in the control of migrasome formation by regulating retraction fibers.

FA-modified-GO coated core–shell Ag₂S@mesoporous silica where DOX was loaded for active targeting FL/PA imaging and synergistic chemo-photothermal therapy of tumors.

IFITM protein is the cells first line of antiviral defense that blocks early stages of viral replication; the underlying mechanism might be associated with the proper distribution in cells. The palmitoylation/depalmitoylation cycle can dynamically regulate protein localization, stability, and function.

Early endosomes are the sorting hub on the endocytic pathway, wherein sorting nexins (SNXs) play important roles for formation of the distinct membranous microdomains with different sorting functions. Tubular endosomes mediate the recycling of clathrin-independent endocytic (CIE) cargoes back toward the plasma membrane. However, the molecular mechanism underlying the tubule formation is still poorly understood. Here we screened the effect on the ARF-6-associated CIE recycling endosomal tubules for all the SNX members in Caenorhabditis elegans (C. elegans). We identified SNX-3 as an essential factor for generation of the recycling tubules. The loss of SNX-3 abolishes the interconnected tubules in the intestine of C. elegans. Consequently, the surface and total protein levels of the recycling CIE protein hTAC are strongly decreased. Unexpectedly, depletion of the retromer components VPS-26/-29/-35 has no similar effect, implying that the retromer trimer is dispensable in this process. We determined that hTAC is captured by the ESCRT complex and transported into the lysosome for rapid degradation in snx-3 mutants. Interestingly, EEA-1 is increasingly recruited on early endosomes and localized to the hTAC-containing structures in snx-3 mutant intestines. We also showed that SNX3 and EEA1 compete with each other for binding to phosphatidylinositol-3-phosphate enriching early endosomes in Hela cells. Our data demonstrate for the first time that PX domain-only C. elegans SNX-3 organizes the tubular endosomes for efficient recycling and retrieves the CIE cargo away from the maturing sorting endosomes by competing with EEA-1 for binding to the early endosomes. However, our results call into question how SNX-3 couples the cargo capture and membrane remodeling in the absence of the retromer trimer complex.

Both the mechanosensitive vimentin cytoskeleton and endocytic caveolae contribute to various active processes such as cell migration, morphogenesis, and stress response. However, the crosstalk between these two systems has remained elusive. Here, we find that the subcellular expression between vimentin and caveolin-1 is mutual exclusive, and vimentin filaments physically arrest the cytoplasmic motility of caveolin-1 vesicles. Importantly, vimentin depletion increases the phosphorylation of caveolin-1 on site Tyr14, and restores the compromised cell migration rate and directionality caused by caveolin-1 deprivation. Moreover, upon hypo-osmotic shock, vimentin-knockout recovers the reduced intracellular motility of caveolin-1 vesicles. In contrary, caveolin-1 depletion shows no effect on the expression, phosphorylation (on sites Ser39, Ser56, and Ser83), distribution, solubility, and cellular dynamics of vimentin filaments. Taken together, our data reveals a unidirectional regulation of vimentin to caveolin-1, at least on the cellular level.

There has been a consensus that actin plays an important role in scission of the clathrin-coated pits (CCPs) besides the large GTPase Dynamin in metazoan cells. However, the recruitment, regulation, and functional interdependence of actin and Dynamin during this process remain inadequately understood. Here, based on small-scale screen and in vivo live-imaging techniques, we identified a novel set of molecules underlying CCP scission in the multicellular organism Caenorhabditis elegans. We found that loss of Wiskott−Aldrich syndrome protein (WASP)-interacting protein (WIP-1) impaired CCP scission, which is independent of WASP/N-WASP (WSP-1) and mediated by direct binding to G-actin. Moreover, the cortactin binding domain of WIP-1 serves as the binding interface for DBN-1/mAbp1, another actin-binding protein. We demonstrate that the interaction between DBN-1 and F-actin is essential for Dynamin-1 recruitment at endocytic sites. In addition, the recycling regulator RME-1/Eps15 homology (EH) domain-containing proteins is increasingly recruited at the arrested endocytic intermediates induced by F-actin loss or Dynamin-1 inactivation, which further stabilizes the tubular endocytic intermediates. Our study provides new insights into the molecular network underlying F-actin participation in the scission of CCPs.