Journal
JOURNAL OF IMMUNOLOGY
Volume 178, Issue 11, Pages 7199-7210Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.178.11.7199
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Funding
- NCI NIH HHS [F32 CA105862, 1F32CA105862-01] Funding Source: Medline
- NIAID NIH HHS [R01 AI034893, 5R01AI034893-13, 5K08AI057999, K08 AI057999, K08 AI057999-04] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [F32CA105862] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [K08AI057999, R01AI034893] Funding Source: NIH RePORTER
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Immature dendritic cells (DCs) capture exogenous Ags in the periphery for eventual processing in endolysosomes. Upon maturation by TLR agonists, DCs deliver peptide-loaded class II MHC molecules from these compartments to the cell surface via long tubular structures (endolysosomal tubules). The nature and rules that govern the movement of these DC compartments are unknown. In this study, we demonstrate that the tubules contain multiple proteins including the class II MHC molecules and LAMP1, a lysosomal resident protein, as well as CD63 and CD82, members of the tetraspanin family. Endolysosomal tubules can be stained with acidotropic dyes, indicating that they are extensions of lysosomes. However, the proper trafficking of class II MHC molecules themselves is not necessary for endolysosomal tubule formation. DCs lacking MyD88 can also form endolysosomal tubules, demonstrating that MyD88-dependent TLR activation is not necessary for the formation of this compartment. Endolysosomal tubules in DCs exhibit dynamic and saltatory movement, including bidirectional travel. Measured velocities are consistent with motor-based movement along microtubules. Indeed, nocodazole causes the collapse of endolysosomal tubules. In addition to its association with microtubules, endolysosomal tubules follow the plus ends of microtubules as visualized in primary DCs expressing end binding protein 1 (EB1)-enhanced GFP.
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