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Local Cytoskeletal and Organelle Interactions Impact Molecular-motor- Driven Early Endosomal Trafficking

Overview
Journal Curr Biol
Publisher Cell Press
Specialty Biology
Date 2013 Jun 18
PMID 23770188
Citations 76
Authors
Affiliations
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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.

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