The tissue-specific expression of TRPML2 (MCOLN-2) gene is influenced by the presence of TRPML1.
The tissue-specific expression of TRPML2 (MCOLN-2) gene is influenced by the presence of TRPML1.
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DOI：
10.1007/s00424-009-0716-5
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发表时间：
2009-11
期刊：
影响因子：
--
通讯作者：
Cuajungco MP
中科院分区：
文献类型：
--
作者：
Samie MA;Grimm C;Evans JA;Curcio-Morelli C;Heller S;Slaugenhaupt SA;Cuajungco MP
Mucolipidosis type IV is a lysosomal storage disorder caused by the loss or dysfunction of the mucolipin-1 (TRPML1) protein. It has been suggested that TRPML2 could genetically compensate (i.e., become upregulated) for the loss of TRPML1. We thus investigated this possibility by first studying the expression pattern of mouse TRPML2 and its basic channel properties using the varitint-waddler (Va) model. Here, we confirmed the presence of long variant TRPML2 (TRPML2lv) and short variant (TRPML2sv) isoforms. We showed for the first time that, heterologously expressed, TRPML2lv-Va is an active, inwardly rectifying channel. Secondly, we quantitatively measured TRPML2 and TRPML3 mRNA expressions in TRPML1−/− null and wild-type (Wt) mice. In wild-type mice, the TRPML2lv transcripts were very low while TRPML2sv and TRPML3 transcripts have predominant expressions in lymphoid and kidney organs. Significant reductions of TRPML2sv, but not TRPML2lv or TRPML3 transcripts, were observed in lymphoid and kidney organs of TRPML1−/− mice. RNA interference of endogenous human TRPML1 in HEK-293 cells produced a comparable decrease of human TRPML2 transcript levels that can be restored by overexpression of human TRPML1. Conversely, significant upregulation of TRPML2sv transcripts was observed when primary mouse lymphoid cells were treated with nicotinic acid adenine dinucleotide phosphate, or N-(2-[p-bromocinnamylamino]ethyl)-5-isoquinoline sulfon-amide, both known activators of TRPML1. In conclusion, our results indicate that TRPML2 is unlikely to compensate for the loss of TRPML1 in lymphoid or kidney organs and that TRPML1 appears to play a novel role in the tissue-specific transcriptional regulation of TRPML2.
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DOI：
10.1073/pnas.0709846104
发表时间：
2007-12-04
影响因子：
11.1
作者：
Grimm, Christian;Cuajungco, Math P.;Heller, Stefan
通讯作者：
Heller, Stefan
影响因子：
5.3
作者：
Dietrich, A;Schnitzler, MMY;Birnbaumer, L
通讯作者：
Birnbaumer, L
影响因子：
4.5
作者：
Cuajungco, Math P.;Samie, Mohammad A.
通讯作者：
Samie, Mohammad A.
DOI：
10.1083/jcb.200904073
发表时间：
2009-07-27
期刊：
The Journal of cell biology
影响因子：
--
作者：
Brailoiu E;Churamani D;Cai X;Schrlau MG;Brailoiu GC;Gao X;Hooper R;Boulware MJ;Dun NJ;Marchant JS;Patel S
通讯作者：
Patel S
影响因子：
7.7
作者：
Bai, Chang-Xi;Giamarchi, Aurelie;Delmas, Patrick
通讯作者：
Delmas, Patrick