TMEM203 Is a Novel Regulator of Intracellular Calcium Homeostasis and Is Required for Spermatogenesis

被引：25

作者：

Shambharkar, Prashant B. ^{[1
]}

Bittinger, Mark ^{[1
]}

Latario, Brian ^{[1
]}

Xiong, ZhaoHui ^{[1
]}

Bandyopadhyay, Somnath ^{[1
]}

Davis, Vanessa ^{[1
]}

Lin, Victor ^{[1
]}

Yang, Yi ^{[1
]}

Valdez, Reginald ^{[1
]}

Labow, Mark A. ^{[1
]}

机构：

[1] Novartis Inst Biomed Res, Dev & Mol Pathways, Cambridge, MA 02139 USA

来源：

PLOS ONE | 2015年 / 10卷 / 05期

关键词：

ENDOPLASMIC-RETICULUM; SEMINIFEROUS EPITHELIUM; CAENORHABDITIS-ELEGANS; GENE-EXPRESSION; CA2+; BAX; CHANNELS; MOUSE; FERTILITY; APOPTOSIS;

D O I：

10.1371/journal.pone.0127480

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Intracellular calcium signaling is critical for initiating and sustaining diverse cellular functions including transcription, synaptic signaling, muscle contraction, apoptosis and fertilization. Trans-membrane 203 (TMEM203) was identified here in cDNA overexpression screens for proteins capable of modulating intracellular calcium levels using activation of a calcium/calcineurin regulated transcription factor as an indicator. Overexpression of TMEM203 resulted in a reduction of Endoplasmic Reticulum (ER) calcium stores and elevation in basal cytoplasmic calcium levels. TMEM203 protein was localized to the ER and found associated with a number of ER proteins which regulate ER calcium entry and efflux. Mouse Embryonic Fibroblasts (MEFs) derived from Tmem203 deficient mice had reduced ER calcium stores and altered calcium homeostasis. Tmem203 deficient mice were viable though male knockout mice were infertile and exhibited a severe block in spermiogenesis and spermiation. Expression profiling studies showed significant alternations in expression of calcium channels and pumps in testes and concurrently Tmem203 deficient spermatocytes demonstrated significantly altered calcium handling. Thus Tmem203 is an evolutionarily conserved regulator of cellular calcium homeostasis, is required for spermatogenesis and provides a causal link between intracellular calcium regulation and spermiogenesis.

引用

页数：25