Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764435
Title: Investigating the cellular roles of LITAF and CDIP1
Author: Qin, Wenxia
ISNI:       0000 0004 7655 9652
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2016
Availability of Full Text:
Access from EThOS:
Access from Institution:
Abstract:
Mutations in LPS-Induced TNF Activating Factor/Small Integral Membrane Protein of the Late Endosome (LITAF/SIMPLE) cause Charcot-Marie-Tooth (CMT) type 1C disease, an autosomal-dominant demyelinating disorder of the peripheral nervous system. The pathogenesis has not been characterized due to little knowledge about the cellular roles of LITAF. N-terminus of LITAF contains PPXY and P(T/S)AP motifs that interact with E3 ubiquitin ligase Itch/Nedd4 and ESCRT-I subunit TSG101, respectively. C-terminus of LITAF consists of a hydrophobic region bracketed by two proposed "CXXC" zinc knuckles, termed the LITAF-like domain or the SIMPLE-like domain (SLD). Mammalian cells also express an uncharacterized Cell Death Inducing P53 target 1 (CDIP1), which has conserved PPXY and P(T/S)AP motifs as well as the LITAF-like domain. Here, we show that LITAF/CDIP1 belong to a novel class of monotopic integral membrane proteins and localise to multiple endocytic compartments. LITAF/CDIP1 are associated with EGFR-containing endosomes and also interact with HD-PTP. Knockdown of LITAF and CDIP1, affect the morphogenesis of Multivesicular Bodies (MVBs). We also show that LITAF (SLD) localises to the Tubular recycling endosome (TRE). LITAF/CDIP1 depletion cause expanded TRE which is involved in the recycling of Clathrin-independent cargoes. Introducing disease-linked mutations into the LITAF (SLD) abolished its TRE association. Hence, our study proposes that the CMT1C disease is caused due to the malformation of TRE and MVBs.
Supervisor: Woodman, Philip ; Tabernero, Lydia Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.764435  DOI: Not available
Share: