Local cytoskeletal and organelle interactions impact molecular-motor- driven early endosomal trafficking

Curr Biol. 2013 Jul 8;23(13):1173-80. doi: 10.1016/j.cub.2013.05.015. Epub 2013 Jun 13.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biological Transport
  • COS Cells
  • Cell Line
  • Chlorocebus aethiops
  • Cytoplasm / metabolism*
  • Dyneins / metabolism
  • Endoplasmic Reticulum / metabolism
  • Endosomes / metabolism*
  • Epidermal Growth Factor / metabolism
  • Quantum Dots / metabolism
  • Transport Vesicles / metabolism*

Substances

  • Epidermal Growth Factor
  • Dyneins