Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/77774
Title: REGULATION OF INVARIANT CHAIN (CD74) TRAFFICKING IN MATURING DENDRITIC CELLS
Authors: MICHAEL FREDERICK SIMONETTI
Keywords: li, Trafficking, Dendritic cells, NOS2, ER, LAMP1
Issue Date: 22-Oct-2013
Source: MICHAEL FREDERICK SIMONETTI (2013-10-22). REGULATION OF INVARIANT CHAIN (CD74) TRAFFICKING IN MATURING DENDRITIC CELLS. ScholarBank@NUS Repository.
Abstract: The invariant chain li (CD74) aids in the folding of MHC Class II in the ER and then targets it to the endosomal/lysosomal compartments through its two cytoplasmic tail di-leucine based D(E)XXXLI sorting motifs. Substitutions of either of the di-leucines or of Asp2 and Asp3 with alanine abolished the targeting functions and internalization of li. We found that following internalization from the cell surface li trafficked to a LAMP1-negative compartment and that deleting the first N-terminal amino acids of li or substituting Asp6 with alanine increased the internalization rate. We showed that li and ?-adaptin co-immunoprecipitate and that ?-adaptin co-localized with li at the perinuclear region. Intracellular high NOS2 expression confined Ii to the perinuclear region as shown by immunofluorescence and caused a shift of li to the ER-enriched fractions when assessed by subcellular fractionation. NOS2 can bind near the membrane distal motif. This suggests that that NOS2 might retain Ii in the ER region by binding near the DDRDLI motif.
URI: http://scholarbank.nus.edu.sg/handle/10635/77774
Appears in Collections:Master's Theses (Open)

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