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" The mucolipidosis type IV associated protein TRPML1 regulates the expression of TRPML2 "


Document Type : Latin Dissertation
Language of Document : English
Record Number : 54387
Doc. No : TL24341
Call number : ‭1468504‬
Main Entry : Mohammad Ali Samie
Title & Author : The mucolipidosis type IV associated protein TRPML1 regulates the expression of TRPML2\ Mohammad Ali Samie
College : California State University, Fullerton
Date : 2009
Degree : M.S.
student score : 2009
Page No : 116
Abstract : Mucolipidosis type IV is a neurodegenerative lysosomal storage disorder caused by dysfunction or lost of TRPML1 protein. TRPML1 belongs to a newly discovered subfamily of transient receptor potential (TRP) cation channels called mucolipin (TRPML). The TRPML subfamily consists of TRPML1, -2 and -3 proteins. Several reports have shown that TRPML2 may be able to compensate for the loss of function phenotype of TRPML1. In this report the possibility that TRPML2 could possibly compensate for the loss of TRPML1 function was investigated both in vivo and in vitro by quantitatively determining the expression levels of TRPML2 in a knockout TRPML1 mouse model (TRPML1-/- ) and in knockdown TRPML1 human cell lines, respectively. TRPML2 was predominantly expressed in the mouse lymphoid organs and kidney, where the endogenous expression level of TRPML2 was significantly reduced in thymus, spleen and kidney of TRPML1-/- mice compared to wild type littermates. Knocking down TRPML1 by RNA interference in HEK-293 cells resulted in a similar reduction of human TRPML2 expression levels, where the endogenous expression of TRPML2 was restored by over-expression of human TRPML1. In addition, a significant up-regulation of TRPML2 in mouse lymphoid cell cultures was observed when they were treated with known TRPML1 activators, such as NAADP and H89. Altogether, these results indicated that TRPML1 regulates the expression of TRPML2 on a transcriptional level; therefore, they may have a closer functional relationship than was previously shown.
Subject : Biological sciences; Molecular biology; Genetics; Cellular biology; 0369:Genetics; 0307:Molecular biology; 0379:Cellular biology
Added Entry : M. Cuajungco
Added Entry : California State University, Fullerton
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