Local Cytoskeletal and Organelle Interactions Impact Molecular-motor- Driven Early Endosomal Trafficking
Overview
Affiliations
Background: In the intracellular environment, motor-driven cargo must navigate a dense cytoskeletal network among abundant organelles.
Results: We investigated the effects of the crowded intracellular environment on early endosomal trafficking. Live-cell imaging of an endosomal cargo (endocytosed epidermal growth factor-conjugated quantum dots) combined with high-resolution tracking was used to analyze the heterogeneous motion of individual endosomes. The motile population of endosomes moved toward the perinuclear region in directed bursts of microtubule-based, dynein-dependent transport interrupted by longer periods of diffusive motion. Actin network density did not affect motile endosomes during directed runs or diffusive interruptions. Simultaneous two-color imaging was used to correlate changes in endosomal movement with potential obstacles to directed runs. Termination of directed runs spatially correlated with microtubule-dense regions, encounters with other endosomes, and interactions with the endoplasmic reticulum. During a subset of run terminations, we also observed merging and splitting of endosomes, deformation of the endoplasmic reticulum, and directional reversals at speeds up to 10-fold greater than characteristic in vitro motor velocities. These observations suggest that endosomal membrane tension is high during directed run termination.
Conclusions: Our results indicate that the crowded cellular environment significantly impacts the motor-driven motility of organelles. Rather than simply acting as impediments to movement, interactions of trafficking cargos with intracellular obstacles may facilitate communication between membrane-bound compartments or contribute to the generation of membrane tension necessary for fusion and fission of endosomal membranes or remodeling of the endoplasmic reticulum.
A novel bacterial effector protein mediates ER-LD membrane contacts to regulate host lipid droplets.
Angara R, Sadi A, Gilk S EMBO Rep. 2024; 25(12):5331-5351.
PMID: 39333627 PMC: 11624262. DOI: 10.1038/s44319-024-00266-8.
Systems mapping of bidirectional endosomal transport through the crowded cell.
Jongsma M, Bakker N, Voortman L, Koning R, Bos E, Akkermans J Curr Biol. 2024; 34(19):4476-4494.e11.
PMID: 39276769 PMC: 11466077. DOI: 10.1016/j.cub.2024.08.026.
Principles of organelle positioning in motile and non-motile cells.
Kroll J, Renkawitz J EMBO Rep. 2024; 25(5):2172-2187.
PMID: 38627564 PMC: 11094012. DOI: 10.1038/s44319-024-00135-4.
Shen Y, Ori-McKenney K Dev Cell. 2024; 59(12):1553-1570.e7.
PMID: 38574732 PMC: 11187767. DOI: 10.1016/j.devcel.2024.03.022.
Making the connection: How membrane contact sites have changed our view of organelle biology.
Voeltz G, Sawyer E, Hajnoczky G, Prinz W Cell. 2024; 187(2):257-270.
PMID: 38242082 PMC: 11830234. DOI: 10.1016/j.cell.2023.11.040.