Molecular basis for the control of motor-based transport of MHC class II compartments

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Molecular basis for the control of motor-based transport of MHC class II compartments

Type: Doctoral Thesis
Title: Molecular basis for the control of motor-based transport of MHC class II compartments
Author: Rocha, Nuno
Publisher: Department Tumor Biology (NKI), Leiden University Medical Center (LUMC), Leiden University
Issue Date: 2008-10-08
Keywords: Dynein
Endocytosis
Late endosomes
Lysosomes
Niemann-Pick
NPC
ORP1L
Rab7
RILP
Abstract: Antigen presentation by MHC class II is critical for immune responses against pathogens and tumors. Antigen loading occurs primarily in lysosomal-related organelles (LROs) known as MIICs. Ultimately, the MHC II-peptide complexes are transported for cell surface display. Here, we study intracellular transport of MIICs, a poorly understood process in MHC II antigen presentation. We propose that Rab7 lies at the heart of transport by assembling a specific receptor (Rab7-RILP-ORP1L) for the minus end-directed dynein-dynactin motor on the cytosolic face of MIICs/LROs. Full activation of transport requires a second receptor, βIII spectrin. Whereas this model explains how Rab7 controls minus end-directed transport, it does not suffice to explain the characteristic pattern of bidirectional motility exhibited by MIICs/LROs. Here, we propose that cholesterol dictates ORP1L conformation which acts as a switch controlling access of dynein-dynactin to Rab7-RILP, thereby regulating LRO positioning, as observed in NPC disease. Rab7-RILP-ORP1L may also integrate transport and tethering of MIICs/LROs, consecutive processes within the endocytic pathway.
Description: Promotor: J.J. Neefjes
With summary in Dutch
Faculty: LUMC
Citation: Rocha, N., 2008, Doctoral thesis, Leiden University
Handle: http://hdl.handle.net/1887/13136
 

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